CoEege  of  ^IjpgicmniS  anh  ^urgeong 


THEODORE  BERNARD  SACHS,  M.D. 

BORN  AT  DINABURG,  RUSSIA,  MAY  2,  1868 
DIED  APRIL  2,  1916,  CHICAGO 


Sundry  Lectures 

On  the  Medical  Phases  of  Tuberculosis 

Delivered  Before 

The  Robert  Koch  Society  for  the 

Study  of  Tuberculosis 


FROM  FEBRUARY  11,  1913 
TO  APRIL  20,  1916 


PUBLISHED  BY  THE 

CHICAGO  TUBERCULOSIS  INSTITUTE 

MAY  1,  1916 


?'^ 


"R54 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/sundrylecturesonOOrobe 


PREFACE 

The  first  meeting  of  the  Robert  Koch  Society  for  the  Study  of 
Tuberculosis  was  held  on  February  11,  1913,  at  the  City  Club,  of  Chi- 
cago. The  organization  was  at  that  time  known  as  the  "Tuberculosis 
Study  Circle  of  the  Chicago  Tuberculosis  Institute." 

The  Society  was  founded  by  Dr.  Theodore  B.  Sachs,  for  the  pur- 
poses which  he  outlined  in  the  following  reprint  from  the  Journal  of 
the  American  Medical  Association,  January  17,  1914: 

"A  study  of  the  existing  anti-tuberculosis  machinery  in  vari- 
ous cities  discloses  the  absence  of  special  physicians'  associations 
for  the  study  of  the  medical  side  of  the  problem.  The  lack  of 
such  associations  that  would  bring  together,  at  stated  intervals, 
medical  men  interested  in  the  disease  for  the  purpose  of  discuss- 
ing its  important  phases  seems  to  be  a  grave  omission  in  the  gen- 
eral scheme,  considering  the  importance  of  the  medical  profession 
as  a  factor  in  the  anti-tuberculosis  movement,  as  well  as  the  exist- 
ence of  a  large  number  of  medical  questions  pertaining  to 
tuberculosis  on  which  the  collective  judgment  of  the  profession 
can  be  formulated  only  through  continuous  discussion  and  study. 

"To  meet  this  need  all  Chicago  physicians  connected  with 
tuberculosis  sanatoria,  hospitals  and  dispensaries,  as  well  as  med- 
ical men  interested  in  the  study  of  the  disease,  were  invited, 
under  the  auspices  of  the  City  Club,  February  11,  1913,  to  attend 
the  first  meeting  of  the  so-called  'Tuberculosis  Study  Circle.' 

"It  was  planned  that  the  time  between  12:15  and  1  o'clock 
be  given  to  the  luncheon,  and  the  hour  between  one  and  two  to  the 
presentation  of  some  important  medical  phase  of  tuberculosis,  by 
someone  who  has  made  a  thorough  study  of  it. 

"The  success  of  the  first  luncheon  led  to  the  others.  The 
meetings  have  proved  to  be  exceedingly  popular,  bringing  to- 
gether for  the  first  time,  at  regular  intervals,  physicians  inter- 
ested in  the  study  of  tuberculosis, 

"(Signed)     Theodore  B.  Sachs. 
"December,  1914." 

On  January  8,  1914,  the  name  of  the  Study  Circle  was  changed  to 
"The  Robert  Koch  Society  for  the  Study  of  Tuberculosis."  A  week 
later  it  was  chartered,  under  that  name,  with  the  following  organiza- 
tion: 

Charter  members  and  Board  of  Directors : 
Group  One — to  serve  one  year: 

Dr.  Henry  B.  Favill. 

Dr.  Frank  S.  Johnson. 

Dr.  Theodore  B.  Sachs. 


4  PREFACE 

Group  Two — to  serve  two  years : 
Dr.  Ethan  A.  Gray. 
Dr.  John  Ritter. 
Group  Three — to  serve  three  years: 
Dr.  James  Alexander  Harvey. 
Dr.  0.  W.  McMiehael. 
President — Dr.  Theodore  B.  Sachs. 
Vice-President — Dr.  O.  W.  McMiehael. 
Secretary-Treasurer — ^Dr.  John  Ritter. 

At  the  meeting  of  October  18,  1915,  Dr.  Sachs  stated  that  he  was 
compelled,  because  of  the  large  amount  of  work  he  had  on  hand,  to 
relinquish  the  office  of  President  of  the  Society.  Dr.  John  Ritter,  the 
present  President,  succeeded  him  in  that  capacity. 


The  organization,  in  Chicago,  of  the  "Robert  Koch  Society  for  the 
Study  of  Tuberculosis ' '  was  conceived  in  the  fertile  brain  of  its  founder, 
the  late  Dr.  Theodore  B.  Sachs. 

From  its  very  inception  it  was  intended  only  as  an  auxiliary  or 
affiliated  society  of  the  Chicago  Tuberculosis  Institute. 

The  primary  object  of  its  creation  was  to  supply  to  a  community  in 
need  of  definite  and  exact  knowledge  concerning  that  widespread  dis- 
ease, tuberculosis,  a  readily  accessible  means  for  studying  it  in  its  en- 
tirety. 

Soon  after  its  organization,  through  the  instrumentality  of  the 
Executive  Committee  of  the  Chicago  Tuberculosis  Institute,  a  charter 
was  asked  for  and  granted  by  the  State  of  Illinois,  and  the  Society  has 
ever  since  been  subject  to  the  laws  governing  the  mother  institution,  the 
Chicago  Tuberculosis  Institute. 

The  founder  and  his  associates  have  always  recognized  this  impor- 
tant fact,  that  to  acquire  definite  knowledge  in  relation  to  this  disease 
a  most  intensive  study  of  the  various  subjects  from  different  angles  is 
necessary,  and  that  the  study  must  include  all  the  medical  aspects.  With 
this  object  clearly  crystallized  in  their  minds,  physicians,  nurses,  social 
workers  and  all  such  of  the  laity  as  were  deeply  interested  in  these 
topics  were  from  time  to  time  invited  to  attend  these  study  hours. 

A  very  live  interest  in  these  study  hours  has  been  manifest  from  the 
very  beginning,  with  a  large  attendance  at  each  meeting. 

This  little  volume  embraces  a  collection  of  the  lectures  given  at  the 
eighteen  meetings,  i.  e.,  from  February  11,  1913,  to  April  20,  1916. 
Unfortunately,  only  an  abstract  can  be  given  in  a  few  instances,  be- 


PREFACE  D 

cause  no  stenographic  notes  were  made  of  those  particular  addresses. 
For  the  later  ones  we  have  had  complete  notes. 

The  lectures  are  arranged  in  the  order  in  which  they  were  delivered, 
no  attempt  having  been  made  at  a  systematic  or  progressive  tabulation — 
because  this  collection  is  not  intended  to  be  a  textbook  nor  a  compen- 
dium on  tuberculosis.  Its  purpose  is  that  of  a  ready  reference,  as  a 
companion  for  the  busy  tuberculosis  worker  who  is  in  need  of  reliable 
information  relative  to  special  tuberculosis  questions. 

It  should  always  be  borne  in  mind  that  this  collection  of  papers  on 
tuberculosis  work  in  the  present  ranks  of  the  present  time,  and  is,  as 
may  be  understood,  subject  to  such  slight  changes  as  may  be  commen- 
surate with  a  better  interpretation  of  many  still  obscure  points. 

If  the  distribution  of  these  papers  should  be  the  means  of  clearing 
up  many  obscure  points  and  the  reader  conceives  a  better  understand- 
ing of  this  important  topic,  enabling  him  to  do  better  and  more  efficient 
work  in  the  field  of  tuberculosis,  to  give  greater  comfort  to  those  suf- 
fering from  this  disease,  then  the  Robert  Koch  Society  will  feel  that  it 
has  been  well  rewarded  for  its  work. 

(Signed)     John  Ritter,  M.D., 
President  of  the  Robert  Koch  Society. 

Chicago,  111.,  May  1,  1916. 


To  all  the  active  tuberculosis  workers  of  our 
country,  to  the  physicians,  the  nurses,  the  social 
workers,  to  the  various  charitable  beneficial  organiza- 
tions associated  in  tuberculosis  work,  to  the  noble 
men  and  women  who  are  ever  ready  with  heart  and 
hand  to  assist  the  unfortunate  tuberculous,  this  col- 
lection of  addresses  on  special  tuberculosis  topics 
is  affectionately  dedicated. 

CHICAGO  TUBERCULOSIS  INSTITUTE. 


TABLE  OF  CONTENTS 

MEETINGS   OF  THE   EOBEET   KOOH   SOCIETY   AND   THE 
SUBJECTS  DISCUSSED 

February,  11,  1913— "Ohemotherapy  of  Tuberculosis"         9 

Prof.  H.  Gideon  Wells,  Director  of  Sprague  Memorial  Institute,  University 
of  Chieago. 

February  28,  1913 — "In  What  Class  of  Cases  Should  We  Use  Tuberculin,  Par- 
ticularly in  Dispensary  Practice?"     (Not  included)* 

General  Discussion. 

March  21,  1913 — "The  Treatment  of  Pulmonary  Tuberculosis  With  Artificial 

Pneumothorax" 13 

Dr.  W.  A.  Gekler,  Associate  Medical  Director,  Chicago  Municipal  Tubercu- 
losis Sanitarium. 

April  16,  1913 — "Some  Phases  of  Immunity,  With  Special  Eeference  to  Tuber- 
culosis."  (Abstract) 21 

Prof.  Ludwig  Hektoen,  University  of  Chicago. 

June  16,  1913 — "Therapeutic  Use  of  Tuberculin."    (Abstract) 21 

Dr.  Charles  L.  Minor,  Asheville,  N.  C. 

October  23,  1913 — "Pneumothorax  in  the  Treatment  of  Tuberculosis"     ...     23 
Dr.  John  B.  Murphy,  Northwestern  University  Medical  School,  and  Dr, 
Philip  Kreuscher,  Chicago. 

November  20,  1913— "The  Present  Status  of  Tuberculin  Therapy"     ....     27 
Dr.  Louis  Hamman,  Johns  Hopkins  University,  Baltimore,  Md. 

January  8,  1914 — "The  Eelation  of  Bacterial  Metabolism  to  Bacterial  Infec- 
tion."    (Not  included)* 

Dr.  Arthur  I.  Kendall,  Professor  of  Bacteriology,  Northwestern  University 
Medical  School,  Chicago. 

March  26,  1914 — "X-Eay  Diagnosis  of  Tuberculosis  of  the  Lungs  and  Bronchial 

Glands."     (Abstract)  34 

Dr.  HoUis  E.  Potter,  St.  Luke's  Hospital,  Chicago. 

Discussion  by  Dr.   James  T.   Case,   Battle   Creek,   Mich.,   and  Dr.   F.   C. 
Turley,  Chicago. 

April  9,  1914 — "Eelative  Importance  of  Bovine  and  Human  Sources  of  Infec- 
tion in  the  Production  of  Tuberculosis" 38 

Dr.  M.  P.  Eavenel,  Professor  of  Bacteriology,  University  of  Missouri,  Co- 
lumbia, Mo. 

June  19,  1914 — "Present  Status  of  Immunization  Against  Tuberculosis"     .      .     45 
Dr.  Gerald  B.  Webb,  Consulting  Physician  Cragmor  Sanatorium  and  Sun- 
nyrest  Sanatorium,  Colorado  Springs,  Colo. 

July  16,  1914 — "Etiology  and  Morbid  Anatomy  of  Bone  and  Joint  Tubercu- 
losis"          50 

Dr.  Charles  M.  Jacobs,  University  of  Chieago. 
"Non-Operative  Treatment  of  Tuberculosis  of  Bones  and  Joints"     ...     54 
Dr.  John  L.  Porter,  University  of  Chicago. 

"Surgical  Treatment  of  Tuberculosis  of  Bones  and  Joints" 57 

Dr.  Edwin  W.  Eyerson,  Eush  Medical  College 

Discussion:     Dr.  John  Eidlon,  Northwestern  University  Medical  School. 

*  No  stenographic  report  made.  7 


8  TABLE   OF    CONTENTS 

September  16,  1914 — "Non-Tuberculous  Lesions  Occurring  in  Tuberculosis"     .     60 
Dr.  Joseph  Zeisler,  Northwestern  University  Medical  School. 

"Tuberculous   Lesions" 62 

Dr.  Oliver  S.  Ormsby,  Eush  Medical  College. 

"Treatment  of  Cutaneous  Tuberculosis" 65 

Dr.  William  A.  Pusey,  University  of  Illinois. 

Discussion:     Dr.  Theodore  B.  Sachs,  Dr.  Joseph  Zeisler. 

October  29,  1914 — "The  Larynx  in  the  Early  Stages  of  Pulmonary  Tubercu- 
losis"          69 

Dr.  Elmer  L.  Kenyon,  Eush  Medical  College. 

"Symptoms  and  Diagnosis  of  Laryngeal  Tuberculosis" 72 

Dr.  E.  Fletcher  Ingals,  Eush  Medical  College. 

"Prognosis  and  Treatment  of  Laryngeal  Tuberculosis" 76 

Dr.  Norval  H.  Pierce,  University  of  Illinois. 

"Prognosis  and  Treatment  in  Laryngeal  Tuberculosis" 79 

Dr.  G.  A.  Torrison,  Eush  Medical  College. 

March  25,  1915 — "Pregnancy  and  Tuberculosis" 81 

Dr.  Charles  S.  Bacon,  University  of  Illinois. 

"Pregnancy    and    Tuberculosis"         86 

Dr.  Joseph  DeLee,  Northwestern  University  Medical  School. 

October  18,  1915 — "Clinical  Symptoms  and  Physical  Signs  in  Early  Diagnosis 

of    Tuberculosis" 92 

Dr.  F.  M.  Pottenger,  Medical  Director  of  Pottenger  Sanatorium,  Monrovia, 
California. 

Jainuary  19,  1916 — "Complement  Fixation  in  Tuberculosis" 103 

Dr.  H.  J.  Corper,  Municipal  Tuberculosis  Sanitarium,  Chicago. 

February  17,  1916 — "Tuberculosis  of  the  Kidney" 112 

Dr.  Herman  L.  Kretschmer,  Eush  Medical  College. 

March  17,   1916 — "The  Specific  Eoentgen  Markings  Characteristic   of  Pulmonary 
Tuberculosis" 120 


Dr.  Kennon  Dunham,  University  of  Cincinnati. 

11  20,  1916 — "The  Lymphatics  and  Lymph 

Eelation  to  Disease  Processes"     . 
Dr.  W.  S.  Miller,  University  of  Wisconsin. 


April  20,  1916 — "The  Lymphatics  and  Lymphoid  Tissue  of  the  Lung  and  Their 
Eelation  to  Disease  Processes" 123 


THE  CHEMOTHERAPY  OF  TUBERCULOSIS 

By  H.  Gideon  Wells,  M.D. 

CHICAGO 

The  principles  of  chemotherapy,  as  laid  down  by  Ehrlich,  are  of 
so  fundamental  a  character  that  there  is  no  limit  to  their  application  in 
infectious  diseases,  and  possibly  in  cancer.  With  the  spirilloses  and 
trypanosome  infections  in  which  most  of  the  work  has  so  far  been  done, 
the  conditions  are  favorable  for  the  meeting  of  the  drug  and  the  germ, 
since  in  most  forms  of  these  diseases  the  germ  lives  chiefly  in  the  blood. 
It  is  noteworthy  that  the  only  disease  in  which  therapia  magna  sterili- 
sans  has  been  practiced  successfully  on  an  empirical  basis  is  also  a 
blood  infection,  malaria.  The  consideration  of  tuberculosis  from  the 
standpoint  of  chemotherapy  brings  in  distinctly  new  problems  owing 
to  the  fact  that  the  bacteria  are  largely  located  in  points  specifically 
removed  from  the  circulation  by  proliferating  tissues.  This  avascularity 
must  of  necessity  have  a  large  influence  on  the  meeting  of  the  drug  and 
the  germ,  and  this  has  perhaps  been  responsible  for  the  lack  of  success 
of  innumerable  empirical  attempts  at  chemotherapy  which  have  been 
made  with  this  disease  in  the  past.  Avascularity  of  an  infected  tissue 
may  make  for  either  assistance  or  hindrance  in  chemotherapy,  for  we  can 
imagine  that  the  drug  may  accumulate  in  the  avascular  area,  just  as, 
for  instance,  calcium  salts  do,  or,  entering  avascular  and  vascular  tissue 
alike,  it  might  remain  longer  where  there  is  no  circulation.  Certain 
drugs  may  be  either  destroyed  or  activated  by  living  cells,  and  hence 
have  either  a  greater  or  less  effect  in  necrotic  portions  of  the  tubercle 
than  elsewhere  in  the  body.  To  attack  the  problem  of  tuberculosis 
chemotherapy  it  seems  necessary  to  learn  first  just  to  what  extent  dif- 
ferent classes  of  chemicals  enter  tubercles,  both  early  and  advanced,  how 
much  they  tend  to  accumulate  specifically  in  tissues  and  how  long  they 
remain  there.  For  a  chemical  which  is  to  destroy  the  tubercle  bacillus, 
it  would  seem,  should  be  one  that  will  enter  readily  avascular  tuberculous 
lesions,  and,  if  possible,  enter  or  accumulate  in  such  tissues  more  than 
in  normal  tissues. 

The  problem  is  further  complicated  by  the  chemical  composition  of  the 
tubercle  bacillus,  with  its  resistant  fatty  and  waxy  material,  which 
must  make  its  permeation  and  destruction  a  very  different  matter  from 
the  attack  of  the  other  naked  and  delicate  trjT)anosomes,  spirillae  and 
spirochaetes.  In  the  investigation  of  the  subject,  the  fatty  matter  of 
the  tubercle  baciUus,  while  perhaps  an  obstacle  to  chemotherapy,  makes 
attacks  of  the  problem  appear  easier,  since  the  permeability  of  the 
bacteria  would  seem  largely  determined  by  this  substance,  which  can 
be  extracted  from  them  in  large  amounts  and  rendered  available  for 
experimental  work  in  vitro,  without  at  the  beginning  calling  for  exten- 
sive animal  experimentation.    The  influence  of  the  fatty  constituent  of 


10  THE   CHEMOTHERAPY   OP   TUBERCULOSIS 

the  cells  upon  the  permeability  of  tissue  cells  to  drugs  and  dyes  has 
already  been  extensively  investigated,  and  we  have  many  clues  for 
investigation  of  the  permeability  of  the  B.  tuberculosis.  We  have  found 
it  possible  to  attack  directly  some  of  the  problems  involved,  while  others 
have  called  for  preliminary  studies  of  certain  fundamental  questions. 

A  study  of  the  permeability  of  tuberculous  lesions  demonstrated  that 
they  behave  like  simple  colloids  in  this  respect,  permitting  crystalloids 
to  diffuse  readily  through  them,  but  being  little,  if  at  all,  permeable  to 
certain  large  coUoidal  molecules.  These  facts  were  determined  in  the 
following  way :  Guinea  pigs  and  rabbits  with  tuberculous  lesions  were 
injected  with  various  iodine  compounds,  and  after  varying  periods  the 
animals  were  bled  to  death  and  the  blood  and  tissues  analyzed  for 
iodine.  The  blood  practically  always  contains  more  iodine  than  any 
tissue  or  organ,  whether  normal  or  tuberculous.  The  liver  usually 
contains  about  one-third  as  much  iodine  per  gram  as  the  blood,  the 
spleen  about  the  same  as  the  liver,  the  lungs  a  little  less,  the  muscle 
about  one-eighth  to  one-tenth  as  much  as  the  blood.  The  kidney,  how- 
ever, as  a  rule,  has  as  large  a  proportion  as  the  blood,  and  more  during 
active  secretion. 

The  effects  of  pathological  changes  upon  the  tissues  were  very  definite. 
Tuberculous  lymph-glands,  as  0.  Loeb  first  showed,  take  up  relatively 
more  iodine  from  the  blood  than  do  the  liver,  spleen,  and  the  lungs  of 
the  same  animal.  When  the  caseous  material  was  abundant  enough  to 
permit  of  separation  from  the  rest  of  the  gland,  it  contained  much  more 
iodine  than  did  the  non-caseous  portion  of  the  gland,  as  is  seen  in 
Experiments  4,  5,  and  14 : 

No.  4  No.  5  No.  14 

Gland  substance 0.295  0.285  0.007 

Caseous  contents 0.481  0.790  0.013 

Tuberculous  lesions  in  the  eye  show,  as  was  also  found  by  Loeb  and 
Michaud  in  four  experiments,  an  increased  capacity  for  taking  up  iodine. 
That  the  entrance  of  iodine  into  tuberculous  tissues  is  not  characteristic 
of  tuberculosis  is  established  by  analysis  of  tissues  of  animals  in  which 
necrosis  and  exudates  were  experimentally  produced.  Of  all  the  tissues, 
the  normal  kidney  alone  seems  to  be  so  permeable  for  iodine  that  it 
comes  to  contain  the  same  proportion  as  the  blood.  If  we  take  muscle 
which  is  not  normally  so  permeable  to  iodine,  we  find  the  interesting 
fact  that  necrotic  areas  in  it  also  tend  to  contain  approximately  as 
much  iodine  as  the  blood.  The  explanation  of  these  results  must  be  as 
follows :  The  partial  impermeability  of  living  cells  is  destroyed  when  the 
cell  is  killed.  Therefore,  the  readily  diffusible  iodine  compounds  pres- 
ent in  the  blood  and  tissue  fluids  will  diffuse  into  necrotic  tissue  elements 
just  as  they  would  diffuse  into  any  inert  water-filled  colloidal  mass,  with 
resulting  tendency  to  approach  osmotic  equilibrium  of  iodine  in  the 
blood  and  necrotic  tissue.  That  it  does  not  depend  upon  chemical  attrac- 
tion or  even  a  specific  physical  absorption  is  shown  by  the  fact  that 


H.    GIDEON   WELLS,   M.D.  11 

if  some  time  is  allowed  for  the  iodine  to  be  excreted  in  part  from  the 
body,  it  leaves  the  necrotic  tissues,  the  blood  and  the  normal  tissues 
pari  passu.  There  is  nearly  always  somewhat  less  iodine  in  inflammatory 
exudates  than  in  the  blood.  The  presence  of  iodine  in  exudates  would 
seem  also  to  be  dependent  entirely  upon  simple  diffusion.  The  high 
iodine  content  in  the  tuberculous  eye  is  presumably  to  be  explained 
as  due  in  part  to  the  inflammatory  exudate  present  and  probably  in  less 
degree  to  necrotic  tuberculous  tissue.  Similarly,  compression  atelectasis 
of  the  lung,  produced  by  pleural  exudates  and  resulting  in  edema  and 
inflammatory  exudate  in  the  alveoli,  is  associated  with  slight  iodine 
increase  in  the  injured  lung.  This  would  seem  to  explain  the  observa- 
tions of  Bondi,  Jacoby,  Fillipi,  Nesti  and  Loeb,  that  drugs  tend  to  enter 
inflammatory  exudates.  Therefore  we  are  led  to  the  conclusion  that 
the  supposed  affinity  of  certain  drugs  for  certain  pathological  tissues 
merely  depends  on  a  decrease  in  the  normal  impermeability  of  diseased 
cells  or  diffusion  into  exudates  in  the  diseased  area,  or  both. 

Necrotic  tissues,  whether  tubercles  or  other  lesions,  behave  like  any 
non-living  colloidal  mass  into  which  crystalloids  diffuse  readily  and 
rapidly,  while  colloids  enter  very  slowly  or  not  at  all.  Possibly  bacteri- 
cidal substances  may  be  found,  which,  like  calcium,  will  tend  to  accumu- 
late in  tuberculous  areas.  The  behavior  of  the  tubercle  bacilli  them- 
selves to  fat-soluble  dyes  has  been  studied  by  Hope  Sherman.  There  is 
a  little  literature  on  staining  of  bacteria  by  fat  dyes,  and  a  prevalent 
belief  that  acid-fastness  depends  largely  or  solely  on  the  wax  of  the 
acid-fast  bacteria.  Miss  Sherman  investigated  the  behavior  of  many 
fat-soluble  and  fat-insoluble  dyes,  and  found  that  in  cultures  of  tubercle 
bacilli  there  is  a  considerable  amount  of  fatty  material  free  between 
the  bacteria  which  readily  stains  with  fat-soluble  dyes,  but  the  dyes  do 
not  stain  the  bacilli  readily,  if  at  all.  On  the  other  hand,  many  dyes 
which  are  insoluble  in  fats,  as  fuchsin,  methylene  blue  and  eosin,  stain 
the  bacilli  readily  and  intensely.  This  determines  that  the  chief  factor 
is  not  the  fatty  content  as  commonly  believed.  Miss  Sherman  found 
that  simply  crushing  bacilli  between  cover-slip  and  slide  deprives  them 
of  their  acid-fastness  and  also  makes  them  permeable  to  fat-soluble 
dyes.  Evidently  fat-solubility  is  not  a  necessary  quality  in  a  substance 
which  is  to  penetrate  the  tubercle  or  the  bacillus,  but  apparently  quite 
the  opposite. 

The  fact  that  water-soluble  dyes  can  penetrate  the  tubercle  bacillus 
adds  much  interest  to  investigations  of  vital  staining  of  tuberculous 
lesions.  Goldmann,  1909,  reported  an  exhaustive  investigation  of  the 
effect  on  the  tissues  of  the  normal  body  of  the  groups  of  vital  stains, 
including  trypan-red,  and  trypan-blue  already  studied  by  Ehrlich  and 
his  co-workers,  comparing  these  with  isamine-blue  and  pyrrol-blue  which 
act  in  a  similar  way.  These  workers,  however,  have  not  taken  up  the 
study  of  the  ehemotherapeutic  value  of  vital  stains  in  tuberculosis, 
although  Goldmann  studied  the  behavior  of  tubercles  in  animals  injected 


12  THE    CHEMOTHERAPY   OF   TUBERCULOSIS 

with  these  dyes.  Recently  a  series  of  papers  has  appeared  dealing  with 
the  so-called  Finkler's  Heilverfahren,  from  the  laboratory  of  the  Grafin 
von  Linden.  This  method  uses  either  methylene-blue  (chloride  of 
iodine)  or  copper  compounds,  or  both.  More  or  less  favorable  results 
were  reported  in  the  few  experimental  animals  tested,  and  also  in  a 
number  of  tuberculous  patients.  Dr.  Lydia  M.  De  Witt  has  investigated 
these  dyes  in  my  laboratory.  She  found  a  considerable  number  of 
dyes  which  penetrate  the  tubercles  readily  and  are  well  borne  by  the 
animals ;  some  dyes  also  penetrate  the  tubercle  bacillus  in  the  lesions  and 
some  have  bactericidal  power  on  these  bacilli  in  vitro.  De  Witt  did  not 
find  any  definite  curative  effects  from  any  of  these  or  other  dyes  in 
infected  tuberculous  guinea-pigs. 

A  rather  spectacular  series  of  papers  has  appeared  by  von  Linden, 
Meissen  and  Strauss,  stating  that  copper  salts  of  various  sorts  have  a 
striking  therapeutic  effect  upon  tuberculosis,  both  of  men  and  experi- 
mental animals.  Our  animal  experimentations  are  totally  in  disagree- 
ment with  the  above  results.  Pekanowich,  who  attempted  to  use  the 
von  Linden  methods  in  patients  with  pulmonary  tuberculosis,  and  his 
colleague  Somagyi,  treated  skin  tuberculosis  with  copper  compounds, 
and  observed  no  favorable  effects. 

In  closing,  a  review  of  recent  studies  of  gold  in  the  chemotherapy 
of  tuberculosis  is  warranted  by  their  highly  interesting  character. 
These,  reported  by  Feldt,  are  based  on  two  observations,  one  made  years 
ago  by  Koch  that  gold  salts  have  a  remarkable  bactericidal  effect  on 
tubercle  bacilli.  This  has  been  corroborated  by  Bruck  and  Glueck,  who 
obtained  decided  therapeutic  effects  by  repeatedly  injecting  gold  and 
potassium  cyanide  intravenously  into  patients  with  lupus.  Feldt  found 
gold  salts  effective  in  dilutions  of  1 :100,000  up  to  1 :2,000,000,  as  con- 
trasted to  copper  salts  which  he  found  ''on  the  border  of  inactivity." 
The  other  basic  observation  is  ascribed  to  Liebreich,  and  is  the  property 
of  cantharidin  to  cause  severe  reactions  in  any  inflammatory  focus. 
This  suggested  to  Spiess  that  cantharidin  might  be  used  as  a  vehicle 
to  gold  in  tuberculous  lesions,  and  experiments  performed  along  this 
line  gave  encouraging  result.  Further  investigations  with  gold  can- 
tharidin preparations  will  be  awaited  with  much  interest. 


THE  TREATMENT  OF  PULMONARY  TUBERCULOSIS 

WITH  ARTIFICIAL  PNEUMOTHORAX 

By  W.  a.  Gekler,  M.D. 

CHICAGO 

Over  one  hiindred  years  ago  Itard,  of  Paris,  first  investigated  the 
causes  of  natural  pneumotliorax.  Some  of  the  symptoms  and  signs  of 
this  condition  had  been  known  since  the  time  of  Hippocrates,  but  it 
remained  for  Itard  to  give  the  first  clear  description  of  a  number  of 
cases  in  which  fluid  and  air  together  occurred  in  the  thorax  during  the 
course  of  pulmonary  disease.  Pneumothorax  had  been  known  several 
centuries  before  Itard 's  time,  usually  as  a  complication  of  stab  wounds 
of  the  chest.  Itard  was  the  first  to  associate  this  condition  with  pul- 
monary disease.  Laennec  gave  us  a  good  description  of  the  physical 
signs  and  symptoms  of  natural  pneumothorax. 

The  occurrence  of  a  spontaneous  pneumothorax  has  long  been  looked 
upon  as  a  practically  fatal  complication  of  an  existing  tuberculosis.  We 
know  that  many  consumptives  die  within  a  few  hours  or  days  after 
the  occurrence  of  an  acute  pneumothorax,  as  a  rule,  suffocation  being 
the  cause  of  death.  "Within  recent  years,  however,  more  and  more 
observers  have  been  reporting  cases  of  spontaneous  tuberculous  pneumo- 
thorax, where  the  condition  was  recognized  promptly  and  treated  con- 
servatively, resulting  in  a  cure.  The  sudden  cessation  of  sputum  and 
fever  in  these  favorable  cases,  along  with  the  improvement  in  the  gen- 
eral condition  and  strength,  led  to  the  advocacy  of  the  artificial  pneumo- 
thorax as  a  means  of  treatment  of  tuberculosis  of  the  lungs.  Carson,  an 
English  physician,  was  the  first,  so  far  as  we  know,  to  suggest  this 
mode  of  treatment  (1821).  Independently  of  him  Spaeth,  a  German 
physician,  made  the  same  suggestion  in  about  1870. 

It  remained  for  Forlanini,  of  Pavia,  to  first  put  this  method  into 
actual  practice.  He  published  his  results  at  the  International  Tubercu- 
losis Congress  in  Eome,  1894.  Murphy,  of  Chicago,  independently  of 
Forlanini,  reported  his  results  in  a  number  of  cases  in  the  American 
Medical  Journal  of  1898.  Lemke,  in  1899,  published  a  preliminary 
report  of  fifty-three  cases  treated  by  him,  in  The  Journal  of  the  Amer- 
ican Medical  Association,  and  at  about  the  same  time  ScheU  published 
his  report  in  the  New  York  Medical  Journal.  For  several  years  after 
Murphy  and  Lemke  reported  their  work,  the  procedure  apparently  fell 
into  disuse  in  this  country.  In  the  last  four  or  five  years  it  has  been 
taken  up  by  a  large  number  of  men  in  different  parts  of  the  country, 
and  seems  to  be  again  gaining  a  firm  foothold  in  all  sections  of  the 
country. 

In  1904,  Brauer,  of  Marburg,  Germany,  began  his  investigations  of 
artificial  pneumothorax,  and  to  him  more  than  anyone  else  we  owe  our 
exact  knowledge  of  this  subject.     He,  with  his  experimental  work  and 


14  ARTIFICIAL   PNEUMOTHORAX 

his  investigations  of  those  cases  which  came  to  autopsy,  worked  out  the 
details  of  this  method  and  put  what  had  been  up  to  this  time  an 
empirical  procedure  on  a  rational  basis.  It  is  to  him  that  we  owe  the 
modern  lung  collapse  therapy  of  tuberculosis.  "While  it  is  true  that  these 
methods  are  only  applicable  in  a  limited  number  of  cases,  yet,  as  he 
himself  says,  these  cases  in  which  we  achieve  success  are  a  net  gain  in 
our  treatment  of  a  disease  which  is  one  of  the  most  difficult  problems 
with  which  we  have  to  contend.  Every  life  saved  by  the  collapse  treat- 
ment is  one  which  would  otherwise  be  lost,  and  this  more  than  justifies 
us  in  making  use  of  this  treatment  wherever  it  is  indicated. 

In  producing  an  artificial  pneumothorax  we  have  two  methods  to 
choose  from,  that  of  Forlandni  and  that  of  Brauer.  Forlanini  simply 
introduces  a  needle  connected  with  a  gas  container  and  a  manometer 
into  the  chest,  relying  on  the  fluctuations  of  the  manometer  to  indicate 
when  he  has  the  point  of  his  needle  between  the  two  pleurae.  The  dis- 
advantage of  the  simple  puncture  is  that  one  cannot  always  tell  with 
certainty  that  the  point  of  the  needle  has  not  penetrated  into  the  lung. 
One  must  of  necessity  work  in  the  dark,  so  to  speak,  and  this  is  not 
without  risk  to  the  patient.  There  have  been  a  number  of  cases  in 
which  sudden  death  from  air  embolus  has  occurred  as  a  result  of  gas 
being  injected  into  one  of  the  pulmonary  veins.  One  must  not  forget 
that  there  is  normally  no  pleural  cavity.  The  visceral  and  costal  pleurae 
are  in  close  apposition,  with  only  a  very  thin  layer  of  fluid  between 
them,  which  acts  as  a  lubricant.  The  exceeding  thinness  of  the  two 
layers  of  pleura  is  reason  enough  why  a  simple  puncture  as  Forlanini 
uses  can  result  in  injury  to  the  lung,  as  well  as  sudden  death.  I  had 
occasion,  while  working  in  the  City  Hospital  of  Frankfort,  Germany, 
to  observe  a  case  which  came  to  autopsy,  and  in  which  an  attempt  had 
been  made  to  produce  artificial  pneumothorax  by  Forlanini 's  method. 
There  was  an  encapsulated  empyema  about  the  size  of  a  goose  egg  at 
the  point  where  the  puncture  had  been  made,  and  this  had  undoubtedly 
been  caused  by  the  puncture  of  a  tuberculous  focus  of  no  small  size 
on  the  surface  of  the  lung.  When  the  needle  penetrates  the  lung,  and 
is  at  the  same  time  fixed  by  the  thoracic  wall  through  which  it  has  been 
thrust,  every  respiratory  movement  must  result  in  tearing  of  the  lung 
tissue.  "We  have  similar  experiences  in  puncturing  the  spleen.  When 
the  lung  is  consolidated  at  the  point  where  the  puncture  is  made,  the 
veins  are  kept  dilated  by  the  consolidated  tissue  surrounding  them,  and 
they  cannot  be  pushed  aside  by  the  needle  as  would  possibly  be  the  case 
in  healthy  lung  tissue.  These  two  facts  make  the  occurrence  of  an  air 
embolus  easy.  The  advantage  of  this  method  of  Forlanini 's  lies  in  its 
simplicity  and  ease,  and  it  is  undoubtedly  much  more  agreeable  to  the 
patient. 

Brauer 's  method  consists  in  laying  bare  the  costal  pleura  at  a  point 
where  one  may  be  fairly  certain  not  to  strike  adhesions,  which  is  usually 
in  the  fifth  or  sixth  interspace  in  the  axillary  region.    An  incision  from 


W.   A.    GEKLER,    M.D.  15 

one  and  one-half  to  two  inches  long  is  quite  sufficient,  and  the  opera- 
tion can  be  carried  out  under  local  anesthesia.  This  method,  while  not 
at  all  difficult  for  one  who  has  even  slight  skill  in  surgery,  entails  the 
strictest  asepsis  and  the  same  attention  to  details  as  a  major  operation. 
It  must  not  be  forgotten  that  a  large  body  cavity  is  being  opened,  and 
infection  may  have  very  serious  consequences. 

The  patient,  as  a  rule,  receives  a  hypodermic  injection  of  a  quarter 
grain  of  morphin  fifteen  or  twenty  minutes  before  the  operation.  I  use 
a  one-half  of  one  per  cent  solution  of  novocain  for  anesthesia,  and  thor- 
oughly infiltrate  the  skin  of  the  area  where  the  incision  is  made.  After 
incising  the  skin  and  superficial  fascia,  all  bleeding  vessels  are  clamped 
off  so  that  the  field  of  operation  is  as  nearly  absolutely  dry  as  possible. 
The  blunt  dissection  of  the  intercostal  muscles  is  often  painful,  but  is 
quickly  accomplished.  When  the  costal  pleura  has  been  laid  bare,  one 
can  see  the  mottled  lung  beneath,  gliding  backward  and  forward  with 
every  respiratory  movement.  A  very  slight  pressure  with  the  blunt 
cannula  causes  a  rupture  of  the  costal  pleura,  and  one  can  hear  the  air 
entering  the  pleura  with  a  hissing  sound.  The  cannula  is  then  tightly 
packed  about  with  damp  sponges  to  keep  any  gas  from  escaping,  and 
before  attaching  the  rubber  tube  from  the  gas  bottle,  I  pass  a  thin 
ureter  catheter  through  the  cannula  as  a  probe  to  give  some  indication 
as  to  whether  the  lung  has  retracted  or  not. 

The  gas  apparatus  consists  of  two  three-liter  bottles,  graduated  at 
every  fifty  and  one  hundred  c.c,  connected  at  the  bottom  with  about  two 
feet  of  rubber  tube,  one  of  the  bottles  being  filled  with  nitrogen  gas  and 
one  with  a  solution  of  bichloride  of  mercury.  The  sublimate  solution 
flowing  into  the  other  bottle  displaces  the  gas  and  forces  it  out  through 
the  tubing  and  cannula  into  the  pleural  cavity.  Between  the  cannula 
and  the  gas  bottle  I  connect,  by  means  of  a  three-way  cock,  a  small 
mercury  manometer,  which  gives  me  the  pressure  under  which  the  gas 
flows  into  the  thorax,  and,  when  the  flow  of  gas  is  stopped,  the  pressure 
I  have  in  the  pneumothorax. 

At  the  first  sitting  I  never  inject  more  than  five  or  six  hundred  c.c. 
of  gas.  In  closing  the  wound,  care  must  be  taken  that  the  intercostal 
muscles  are  tightly  sutured,  so  as  to  prevent  the  occurrence  of  subcu- 
taneous emphysema,  which,  while  annoying,  is  not  dangerous  and  usually 
subsides  within  a  week.  Five  or  six  small  skin  sutures  are  sufficient  to 
close  the  wound,  which  is  then  dressed  in  the  ordinary  manner,  with  no 
drains.  "With  good  asepsis  and  first-class  suture  material,  there  is  no 
danger  of  wound  infection  and  subsequent  empyema. 

The  object  of  this  operation  is  simply  to  produce  a  small  bubble  of 
gas  which  can,  at  later  punctures,  be  enlarged.  I  usually  puncture  the 
first  time  two  or  three  days  after  the  operation.  The  equipment  is 
practically  the  same  as  at  the  first  operation,  with  the  exception  that 
the  sharp  needle  is  substituted  for  the  blunt-pointed  cannula.  It  is 
hardly  necessary  to  say  that  one  does  not  puncture  through  the  wound 


16  ARTIFICIAL   PNEUMOTHORAX 

made  at  the  first  operation,  but  in  one  of  the  interspaces  near  it.  Of 
course,  I  always  make  an  X-ray  examination  to  determine  exactly  the 
size  and  location  of  my  pneumothorax  before  puncturing.  In  this  way 
I  avoid  striking  possible  adhesions  with  my  needle,  and  also  avoid  injur- 
ing the  lung  by  puncturing  too  deeply.  After  the  first  puncture,  I  punc- 
ture every  week,  until  I  notice  by  the  amount  of  gas  necessary  at  each 
injection  that  resorption  is  taking  place  more  slowly,  and  then  the 
intervals  between  punctures  are  lengthened  until,  in  several  months, 
patients  go  two  or  three  weeks  without  further  punctures  being 
necessary. 

It  is  best  to  keep  the  pneumothorax  at  such  a  pressure  that  there 
are  no  respiratory  movements  of  the  collapsed  lung,  which  is  usually 
a  pressure  of  -j-3  to  -|-10  mm.  of  mercury  on  expiration,  and  from 
0  to  +1  or  +2  mm.  on  inspiration.  These  pressures  vary  in  the 
individual  cases  with  the  elasticity  of  the  mediastinum  and  the  degree 
of  collapse  obtained. 

The  production  of  an  artificial  pneumothorax  cannot  be  said  to  be 
an  operation  requiring  an  extraordinary  amount  of  skill,  and  the 
same  can  be  said  of  the  subsequent  injections  of  gas.  The  difficulty 
with  this  mode  of  treatment  lies  in  the  selection  of  cases.  On  this  one 
point  alone  one  finds  great  diversity  of  opinion.  From  the  accounts 
in  the  medical  literature,  and  from  my  own  experience,  I  have  found 
that  the  more  rigidly  one  adheres  to  Brauer's  precepts  the  greater  is 
the  success  attained.  Operative  interference  should  be  reserved  for 
those  cases  in  which  the  usual  sanatorium  treatment  does  not  bring 
success.  Strictly  incipient  cases  should,  of  course,  not  be  treated  sur- 
gically. A  proportion  of  the  moderately  advanced  cases  will  also  respond 
readily  to  non-surgical  treatment.  We  have,  however,  a  number  of 
advanced  and  far  advanced  cases  in  which  the  disease  seems  to  show  no 
inclination  to  heal,  in  spite  of  anything  one  can  do.  Cavities  of  any 
appreciable  size  very  seldom  can  be  made  to  heal  without  surgical  inter- 
ference. In  these  cases,  where  the  active  disease  is  limited  to  one  side, 
one  is  justified  in  attempting  the  pneumothorax  treatment.  Laryngeal 
tuberculosis  is  not  a  contra-indication. 

"Where  there  are  active  lesions  in  both  lungs,  artificial  pneumothorax 
on  one  side  is  very  apt  to  cause  the  disease  to  progress  more  rapidly 
on  the  other.  Tuberculosis  of  the  bowels  or  peritoneum  is  an  absolute 
contra-indication  to  operative  interference  with  the  disease  of  the  lung. 
Tuberculosis  of  the  kidneys  and  generalized  tuberculosis  are  also  contra- 
indications. Laryngeal  tuberculosis,  with  great  destruction  of  laryn- 
geal tissues,  makes  artificial  pneumothorax  inadvisable. 

The  greatest  possible  accuracy  in  physical  and  X-ray  examinations  is 
necessary  for  the  proper  selection  of  the  eases.  Very  careful  percussion 
will  almost  always  give  us  approximately  the  extent  of  any  consoli- 
dations. It  is  in  auscultation  that  we  encounter  difficulties  in  the 
advanced  and  far  advanced  cases.  With  changes  in  the  breath  sounds 
and  rales  transmitted  from  one  side  to  the  other  and  transmitted  from 


W.   A.    GEKLER^    M.D,  17 

one  place  on  one  side  over  the  remainder  of  that  side,  it  is  no  wonder 
that  the  examiner  is  occasionally  confused.  Usually  repeated  exam- 
inations are  necessary  to  arrive  at  a  conclusion.  The  greatest  difficulty 
lies  in  the  diagnosis  of  pleuritic  adhesions.  In  some  cases,  where  there 
is  a  history  of  a  previous  pleurisy,  and  where,  on  physical  and  X-ray 
examination,  there  is  very  little,  if  any,  opening  up  of  the  comple- 
mentary space,  one  is  occasionally  surprised  to  find  at  operation  few  or 
no  adhesions.  In  other  cases,  where  careful  physical  and  X-ray  exam- 
inations do  not  reveal  any  evidences  of  pleuritic  adhesions,  it  may,  at 
operation,  be  absolutely  impossible  to  inject  any  gas  between  the  pleura. 
Sometimes,  after  exposing  the  costal  pleura,  the  lung  may  be  seen  glid- 
ing back  and  forth  beneath,  and  yet  small,  thread-like  adhesions  may 
exist  in  sufficient  number  to  hinder  a  coUapse  of  the  lung. 

The  examination  with  the  X-ray  is  fuUy  as  important  as  the  physical 
examination.  As  a  rule,  I  make  one  large  plate  of  the  entire  chest  and 
a  smaller  one  of  only  the  apices.  In  addition  to  this,  the  examination 
with  the  fluorescent  screen  shows  the  movability  of  the  diaphragm,  and 
has  the  advantage  over  the  plates  in  that  one  can  turn  the  patient  in 
any  position  one  wishes,  and  often  get  a  more  accurate  idea  of  the  exact 
location  of  larger  consolidations  and  cavities.  The  plates  show  much 
greater  detail  and  bring  out  things  that  cannot  be  detected  with  the 
screen.  They  are,  of  course,  a  permanent  record,  and  can  be  examined 
and  studied  with  more  thoroughness  than  a  screen  examination  of  a 
patient  would  allow.  It  would  obviously  be  impossible  to  keep  a  patient 
before  an  X-ray  tube  for  ten  or  fifteen  minutes,  on  account  of  the  danger 
of  X-ray  burns,  and  on  account  of  the  fact  that  no  X-ray  tube  will 
stand  more  than  a  minute  or  two  of  operation  at  a  time,  with  any  con- 
siderable current  going  through  it.  Both  screen  and  plate  examinations 
are  absolutely  indispensable.  We  have  no  other  means  of  locating  deep 
seated  lesions,  although,  of  course,  one  cannot  determine  by  the  X-ray 
examination  whether  or  not  these  lesions  are  active. 

A  considerable  amount  of  healed  trouble  on  the  supposedly  well  side, 
as  indicated  with  the  X-ray,  would  be  a  contra-indication  to  operative 
interference.  It  is  essential  that  the  operator  have  equal  skill  in  X-ray 
as  well  as  physical  diagnosis,  because  neither  one  is  as  serviceable  as 
the  two  in  conjunction.  In  nearly  every  case  the  results  with  one 
method  will  supplement  and  complete  those  obtained  with  the  other. 
Here  I  wish  to  state  that  it  is  only  by  having  frequent  autopsies  to  check 
our  diagnoses  that  we  can  obtain  the  necessary  accuracy.  The  findings 
at  the  autopsy  table  will,  more  than  any  other  one  thing,  teach  us  to 
be  modest  in  our  estimation  of  our  own  skill,  and  correct  habitual  mis- 
takes in  diagnosis. 

The  result  of  the  operation  depends  directly  upon  the  degree  of 
collapse  of  the  lung  one  can  produce.  Where  numerous  adhesions  will 
not  permit  the  larger  part  of  the  lung  to  collapse,  there  is  little  or  no 
change  in  any  of  the  patient's  symptoms.  Where  an  extensive  collapse 
is  produced  the  patient  usually  notices  a  more  or  less  marked  diminution 


18  ARTIFICIAL   PNEUMOTHORAX 

in  the  cough  immediately  following  the  operation.  Usually  there  is  an 
increase  in  the  amount  of  sputum  the  next  day,  to  be  followed  from 
that  time  on  by  a  marked  decrease.  One  occasionally  notices  the  same 
thing  after  the  first  few  punctures.  Sometimes  there  is  also  an  increase 
in  the  fever  immediately  following  the  operation,  due,  no  doubt,  to  the 
toxins  forced  out  of  the  lesion  by  the  compression.  More  often  one 
notices  an  immediate  drop  in  the  temperature,  and,  where  one  has 
secured  a  good  collapse  of  the  lung,  the  fever  will  often  entirely  dis- 
appear within  a  few  days.  Quite  often,  where  there  is  an  increase  in 
the  fever,  any  healed  lesions  that  may  be  present  will  show  signs  of  irri- 
tation, which  disappear  in  the  course  of  several  days,  just  as  in  a  con- 
stitutional tuberculin  reaction. 

When  the  patients  become  free  of  fever  and  the  cough  and  sputum 
are  reduced,  there  naturally  results  a  marked  change  for  the  better  in 
the  general  condition.  The  appetite  improves  and  with  it  the  strength. 
Patients  do  not  always  gain  so  rapidly  in  weight  as  one  might  expect, 
but  they  usually  gain  slowly  and  steadily.  In  several  weeks  they  are 
usually  able  to  be  up  and  about  without  any  noticeable  bad  effect  on 
the  condition  of  the  lung  or  on  the  general  condition.  These  patients 
do  not  notice  any  dyspnea  on  ordinary  exertion  as  one  might  perhaps 
expect.  Circulatory  disturbances  are  also  uncommon.  There  is  no 
noticeable  hypertrophy  of  the  right  heart.  Several  of  these  operative 
cases  have  come  to  autopsy  and  were  reported  by  Graetz.  One  is  struck 
by  the  amount  of  connective  tissue  formation  in  the  lung,  as  compared 
with  other  tuberculous  cases  in  whom  there  has  been  no  operative  inter- 
ference. In  tuberculous  lesions,  as  in  other  lesions,  healing  means  suf- 
ficient formation  of  scar  tissue  to  replace  the  defect.  In  tuberculous 
cases  treated  by  other  methods,  including  various  kinds  of  tuberculin 
and  vaccines,  I  have  never  seen  such  marked  connective  tissue  growth 
in  affected  lungs  as  in  these  operative  cases.  Nor  does  one,  in  ordinary 
cases,  see  these  broad,  flat  scars  indicating  healed  cavities.  Here,  again, 
the  autopsy  table  furnishes  the  final  proof  of  the  value  of  a  method  of 
treatment. 

Why  does  the  collapse  of  a  tuberculous  lung  bring  about  such  marked 
changes  in  the  condition  of  a  patient  1  We  know  that  the  flow  of  lymph 
from  the  lungs  to  the  bronchial  glands,  and  into  the  general  circula- 
tion, is,  to  an  extent,  controlled  by  the  respiratory  movements  of  the 
lung.  Where  the  chest  wall  is  elastic  and  the  diaphragm  unhampered 
in  its  movements,  there  is  possible  the  greatest  amount  of  respiratory 
expansion  and  contraction  of  the  lung,  with  a  corresponding  rapidity 
in  the  flow  of  lymph.  In  any  normal  lung,  the  flow  of  lymph  from  the 
parenchyma  to  the  hilus  is  greatest  in  those  parts  where  the  respiratory 
movements  are  greatest.  In  the  tuberculous  lungs,  the  toxins  are  borne 
from  the  lesion  into  the  general  circulation  in  the  lymphatic  fluid,  and 
the  more  rapid  the  flow  of  lymph,  the  more  toxins  brought  into  the 
general  circulation,  and  the  more  severe  are  the  symptoms  of  this  intox- 
ication. 


W.   A.    GEKLEB,   M.D.  19 

In  the  ordinary  sanatorium  treatment  of  tuberculosis,  we  try  to 
reduce  to  a  minimum  this  absorption  of  toxins,  by  putting  the  patient 
at  as  nearly  absolute  rest  as  possible,  thus  reducing  the  amount  of 
movement  of  the  lungs.  In  inducing  collapse  of  the  lungs  we  go  farther 
still,  in  that  we  almost  entirely  stop  the  lymphatic  flow  by  preventing 
any  respiratory  movements.  There  results  in  the  collapsed  lung,  not 
a  hyperemia  and  stasis,  as  one  might  at  first  expect,  but  an  anemia,  and 
with  it,  of  course,  a  diminution  in  the  amount  of  the  lymphatic  fluid 
in  the  collapsed  organ.  In  other  words,  we  prevent  the  toxins  from 
getting  into  the  general  circulation,  and  causing  the  toxic  symptoms 
which  are  common  to  this  disease.  This  explains  the  cessation  of  fever, 
improvement  in  the  appetite,  and  disappearance  of  such  other  symptoms 
as  may  be  caused  by  this  intoxication,  as,  for  instance,  disturbances 
in  digestion. 

As  remarked  before,  it  is  very  difficult,  with  any  of  the  means  we  now 
have  at  our  command,  to  bring  about  healing  of  a  cavity  that  has  attained 
any  considerable  size.  By  compressing  the  lung,  we  can  often  bring 
the  walls  of  the  cavity  in  apposition,  and  thus  bring  about  complete 
and  permanent  healing.  This  explains  the  great  decrease  in  the  amount 
of  sputum  and,  of  course,  with  it  the  cough  in  these  cases.  Not  only 
that,  but  we  prevent  mechanically  those  movements  of  the  tissue  which 
hinder  formation  of  sear  tissue.  Just  as  we  often  put  tuberculous 
joints  in  plaster  casts  to  prevent  movement  and  permit  a  scar  to  be 
formed,  so  do  we  put  the  lung  in  a  cast  of  gas,  with  the  same  end  in 
view. 

The  question  at  once  arises, — will  these  cases  really  stay  cured,  or 
will  the  disease  continue  to  make  progress,  when  the  lung  is  allowed 
to  expand  again?  I  can  only  relate  what  I  myself  have  seen,  and  say 
that  in  those  cases  where  a  satisfactory  collapse  was  obtained,  the  per- 
manent results,  even  in  advanced  and  far  advanced  cases,  are  often  as 
good  as  those  we  obtain  with  incipient  cases  treated  by  non-surgical 
methods, — in  other  words,  clinical  cure.  I  have  known  women  patients 
to  get  married,  after  having  gotten  weU  from  tuberculosis  with  pneu- 
mothorax treatment,  and  even  go  safely  through  the  ordeal  of  child- 
birth, which  it  seems  to  me  is  as  good  a  test  as  any  we  have.  During 
my  year  and  a  half  as  Brauer's  assistant,  I  had  opportunity  to  see  and 
examine  practically  all  of  his  cases  who  reported  for  re-examination  and 
observation,  and  most  of  them  were  engaged  in  their  usual  avocations, 
only  observing  such  precautions  as  any  intelligent  person  would  observe 
who  was  familiar,  from  personal  experience,  with  a  disease  as  treacher- 
ous as  tuberculosis.  One  of  these  cured  cases  was  an  orderly  in  Brauer's 
clinic,  and  did  quite  as  heavy  manual  labor  as  was  exacted  of  other 
orderlies  who  had  never  been  sick.  It  seems  to  me  that  these  results 
speak  for  themselves. 

As  a  rule,  we  flnd  adhesions  sufficient  to  prevent  satisfactory  col- 
lapse of  the  lungs  in  about  25  per  cent,  of  the  cases  on  whom  we  attempt 


20  ARTIFICIAL   PNEUMOTHORAX 

to  operate.  These  patients,  realizing  the  hopelessness  of  their  condition, 
often  ask  us  to  do  something  for  them,  even  to  the  extent  of  submitting 
them  to  a  dangerous  operation.  In  these  eases  we  can  often  induce  sat- 
isfactory collapse  of  the  lung  by  some  form  of  thoracoplastic  operation. 
The  thoracoplastic  operations  for  producing  collapse  of  the  lung  in 
cases  of  tuberculosis  were  first  advocated  by  Brauer,  although  a  number 
of  surgeons  had  made  attempts  to  treat  cavities  and  tuberculous 
abscesses  of  the  lung  surgically  long  before  his  time.  This  is  not  the 
place  to  go  into  details  concerning  this  work,  but  I  just  wish  to  state 
that  I  have  seen  cases  in  which  sufficiently  satisfactory  collapse  was 
produced  by  such  an  operation  to  result  in  healing  of  the  diseased  lung. 

Among  the  patients  at  the  Indiana  State  Hospital  for  Tuberculosis, 
I  have  made  eleven  attempts  to  induce  artificial  pneumothorax.  In  two 
cases  it  was  absolutely  impossible  to  get  any  gas  into  the  chest,  on  account 
of  very  extensive  adhesions.  In  another  case,  it  was  possible  to  get  a 
small  amount  of  gas  into  the  pleural  space,  but  on  attempting  to  enlarge 
this  small  pneumothorax,  which  was  on  the  left  side,  there  resulted 
circulatory  disturbances,  which  made  it  impossible  to  continue  this  form 
of  treatment.  None  of  these  patients  were  permanently  injured  by  these 
attempts.  In  five  other  cases,  a  partial  collapse  was  secured,  sufficient 
to  result  in  more  or  less  benefit  to  the  patients,  as  evidenced  in  decrease 
of  fever,  cough  and  sputum,  and  betterment  of  the  general  condition. 
I  doubt,  however,  as  to  whether  it  will  be  possible  to  bring  about  heal- 
ing in  all  of  these  five  cases.  The  symptomatic  improvement  has,  so  the 
patients  feel,  more  than  repaid  them  for  having  submitted  to  the 
operation.  In  three  cases,  I  have  been  able  to  get  a  degree  of  collapse 
which,  I  believe,  by  the  progress  we  have  made  up  until  this  time,  will 
result  in  clinical  cures.  In  only  one  of  these  eleven  cases  were  there 
no  adhesions  whatever,  and  a  perfect  collapse  was  possible.  In  Brauer 's 
cases,  there  were  about  40  per  cent,  successes,  a  result  which  is  all  the 
more  wonderful  when  one  considers  that  he,  up  until  a  year  or  so  ago, 
would  only  consent  to  operate  on  the  absolutely  hopeless  cases.  He  now 
takes  the  stand  that  it  is  often  wise  to  operate  on  patients  who  are  not 
so  advanced  as  those  whom  he  has  reported,  and  he  believes  that  a  still 
better  record  can  be  achieved. 

We  have,  then,  another  weapon  to  use  in  our  fight  against  tuber- 
culosis, and  while  its  use  must  of  necessity  be  limited,  it  nevertheless 
can  be  employed  in  saving  lives  that  are  now  hopelessly  lost.  The  col- 
lapse therapy,  whether  it  be  by  means  of  artificial  pneumothorax  or  some 
plastic  operation,  is  entirely  rational,  and  supported  by  clinical  and 
experimental  evidence.  It  has  won  recognition,  both  in  this  country  and 
abroad,  and  can  no  longer  be  ignored.  The  results  of  this  work  and  the 
principles  underlying  it  also  go  to  prove  that  there  is  an  entirely 
mechanical  factor  in  the  growth  of  a  tuberculosis  process,  and  that  this 
factor,  as  well  as  the  theories  of  immunity,  must  be  considered  in 
attempting  to  explain  consumption  of  the  lungs. 


SOME  PHASES  OF  IMMUNITY  WITH  SPECIAL 
REFERENCE  TO  TUBERCULOSIS* 

By  Ludwig  Hektoen,  M.D. 
university  of  chicago 

The  functions  of  antibodies  in  immunity  were  discussed  and  the 
facts  known  in  respect  to  the  formation  of  antibodies  under  natural  and 
experimental  conditions  were  presented  briefly.  Then  the  antigenic 
properties  of  the  tubercle  bacillus  and  the  mechanisms  by  which  the 
body  protects  itself  from  tuberculosis  and  resists  tuberculous  infection 
once  established  were  considered.  Finally  the  treatment  of  tuberculosis 
and  mixed  infection  in  tuberculosis  by  means  of  various  kinds  of  vac- 
cines (including  tuberculins)  was  discussed.  The  importance  of  auto- 
genous vaccines  was  emphasized  and  the  efforts  of  manufacturers  to 
stampede  the  medical  profession  into  the  indiscriminate  use  of  com- 
mercial vaccines  of  various  kinds,  stock  and  polyvalent,  strongly  con- 
demned. 


THERAPEUTIC  USE  OF  TUBERCULIN 

(Abstract) 
By  Charles  L.  Minor,  M.D. 

ASHEVILLE,   N.   C. 

The  first  vial  of  tuberculin  arrived  in  New  York  in  1890,  at  the  time 
of  the  conclusion  of  Dr.  Minor's  interne  service  in  St.  Luke's  Hospital, 
New  York.  He  has  constantly  used  tuberculin  during  the  last  seven 
years,  and  would  be  quite  unwilling  now  to  be  without  it.  He  stated  that 
20  per  cent,  is  the  approximate  number  of  cases  upon  which  it  can  be 
used,  but  that  the  final  word  as  to  the  ultimate  uses  of  tuberculin  is 
still  to  be  spoken  by  sanatorium  and  dispensary  practitioners. 

Of  the  large  number  of  tuberculins,  the  essential  thing  is  that  a 
physician  should  thoroughly  know  one  of  them  and  its  uses.  Per- 
sonally Dr.  Minor  uses  O.T.  chiefly,  and  after  that  B.E.,  B.F.  and  T.R. 

Tuberculin  reduces  by  25  per  cent,  the  likelihood  of  relapse;  it 
improves  the  physical  condition  and  to  a  still  unascertained  degree 
produces  immunity  from  future  attack.  It  produces  a  50  per  cent, 
decrease  in  the  sputum  of  the  patients,  as  compared  with  those  not  being 
so  treated.    Consequently  its  value  is  real.    As  a  parenthesis,  Dr.  Minor 

*  Unfortunately  no  stenographic  report  of  the  lecture  was  made. 

21 


22  THERAPEUTIC    USE   OF   TUBERCULIN 

stated  that  Dr.  Von  Ruck,  of  Asheville,  believes  that  he  has  an  immun- 
izing serum  which  produces  permanent  immunity  in  children. 

Tuberculin  is  not  necessary  in  incipient  cases  but  is  invaluable  in 
eases  of  moderate  involvement,  afebrile  cases  and  those  which  persist 
in  not  making  progress  toward  recovery.  It  is  of  utmost  assistance  in 
laryngeal  cases,  also  in  bone  cases  and  especially  in  unsoftened  glandu- 
lar cases. 

Fever  is  contra-indication,  except  in  the  hands  of  those  thoroughly 
trained  in  the  use  of  tuberculin.  Even  then  it  is  not  for  patients  who 
run  over  100.2  degrees. 

Results  of  injection  must  be  closely  watched  and  dosage  stopped  or 
decreased  upon  appearance  of  local  reaction  (superficial  and  not  deep 
injection,  so  that  focal  signs  may  be  clearly  read).  Loss  of  weight 
usually  indicates  a  period  of  stoppage  with  later  resumption;  tachy- 
cardia or  malaise  indicate  a  suspension  of  dosage.  Blank  doses  may 
well  be  used  to  allay  the  fear  of  timorous  patients.  Among  those  most 
nervous,  reactions  have  occasionally  been  secured  without  the  use  of 
tuberculin  by  administering  a  blank  dose.  Finally  blood-streaked 
sputum  indicates  suspension  of  dosage. 

Two  systems  of  dosage  prevail:  First,  the  gradual  increase  in  size 
of  dose  and,  second,  that  designed  to  secure  a  minimum  reaction.  The 
gradually  increasing  dosage  is  believed  by  Dr.  Minor  to  be  the  better 
practice.  Beginning  with  one  one-millionth  milligram  and  increasing 
gradually,  avoiding  reactions,  he  gives  two  treatments  per  week.  But 
after  the  size  of  the  dose  is  increased,  once  per  week  is  sufficiently  often. 
In  case  of  the  appearance  of  a  local  reaction,  either  repeat  the  same  dose 
or  reduce  it  by  half.  In  case  of  a  focal  reaction,  reduce  it  one-half.  By 
observing  these  two  methods  a  constitutional  reaction  will  be  avoided. 


PNEUMOTHORAX   AND   REST   TREATMENT   IN   THE 
MANAGEMENT  OF  PULMONARY  TUBERCULOSIS 

(Abstract) 

By  John  B.  Murphy,  M.D.,  Chicago,  and 

Philip  Kreuscher,  M.D,.  Chicago 

Rest  as  a  treatment  in  pulmonary  tuberculosis  is  almost  as  old  as 
the  disease  itself.  The  amount  of  improvement  is  in  direct  ratio  to 
the  degree  of  absolute  mental  and  physical  rest  which  the  patient 
obtains.  The  difficulty  encountered  in  enforcing  the  strict  rest  cure  is 
accountable  for  the  period  of  reaction  of  two  decades  ago,  and  con- 
sisted in  mental  and  physical  activity.  This  treatment  was  soon  aban- 
doned in  the  advanced  cases,  on  account  of  disastrous  results.  Clinical 
observation  showed  that  the  body,  when  permitted  to  rest,  was  better 
fitted  to  overcome  the  disease  and  immunize  itself  against  the  toxins. 
Twenty-five  years  ago  Murphy  stated  that  a  patient  with  an  acute 
tuberculosis  of  the  lung  should  be  treated  on  the  same  basis  as  a  typhoid 
case — ^namely,  put  in  bed  absolutely  at  rest,  and  watched  and  dieted 
with  utmost  care.  After  the  patient's  temperature  is  normal  for  a  time, 
he  is  gradually  elevated  in  bed,  and  slowly  increasing  exercise  is  per- 
mitted each  day.  By  graduated  exercise  the  patient  develops  an  auto- 
opsonic  index,  most  favorable  to  repair.  He  walks  about,  begins  to 
do  light  work,  and  finally  manual  outdoor  labor  without  the  slightest 
rise  in  temperature  as  a  result. 

The  principle  of  organ  rest  was  first  conceived  by  Carson,  of  Liver- 
pool, in  1821,  when  he  advanced  the  idea  that  the  diseased  lung  would 
heal  more  quickly  if  the  lung  itself  were  put  at  rest.  Carson  concluded 
from  his  animal  experiments  that  one  lung  may  be  coUapsed  with  per- 
fect impunity.  He  believed,  furthermore,  that  pulmonary  tuberculosis 
could  be  most  successfully  treated  by  * '  mechanical  means. ' '  In  support 
of  this  he  referred  to  several  instances  of  history,  where  in  battle  sol- 
diers received  penetrating  wounds  of  the  chest  wall  and  were  cured  of 
an  existing  tuberculosis.  Parolo  (1849),  Ramadge  (1834),  Constatt 
(1843),  Wundelich  (1856),  Ehlers  (1867),  aU  spoke  of  Carson's  pro- 
posed treatment,  but  there  is  no  report  to  show  that  any  of  them  per- 
formed the  operation  on  the  human.  Porlanini,  of  Padua,  next  wrote 
on  this  subject,  1882.  The  paper, ' '  Surgery  of  the  Lung, ' '  read  by  Mur- 
phy at  the  meeting  of  the  American  Medical  Association,  1898,  and  the 
subsequent  work  by  Murphy  and  Lemke  influenced  Prof.  Brauer  to  take 
up  actively  the  treatment  of  pulmonary  tuberculosis  by  pneumothorax. 
Forlanini  and  other  European  physicians  and  a  number  of  Americans 
began  using  the  method  extensively  and  have  continued  up  to  the  pres- 
ent time. 

Authorities  differ  concerning  the  indications  for  producing  pneu- 
mothorax.    Lenormant  says  American  surgeons  have  advised  employ- 

23 


24  P^TEUMOTHORAX  AND  REST  TREATMENT 

ment  of  artificial  pneumothorax  in  the  beginning  of  the  disease.  Recent 
European  authors,  however,  reserve  this  method  for  chronic  unilateral 
lesions  with  cavity  formations,  in  which  cases  the  efforts  were  unsuc- 
cessful in  a  number  of  cases  on  account  of  pleural  adhesions.  These 
failures  are  rare  in  American  statistics  (Murphy,  4  per  cent,  36 ;  Lemke, 
5  per  cent)  on  account  of  the  fact  that  they  deal  with  cases  in  an  early 
stage.  According  to  Forlanini,  rapid  development  of  the  disease  is  a 
contra-indication,  but  here  again  Brauer  and  Von  Muralt  have  had 
excellent  results.  In  a  recent  article  Gray,  of  Chicago,  reports  sixty- 
one  cases  treated  in  various  stages.  He  prefers  the  incipient  cases 
and  cites  Brauer  and  Spengler's  series  of  eighty-eight  cases  treated  in 
the  late  stages,  with  twenty-three  deaths  and  eight  failures,  and  very 
correctly  makes  the  queries,  "Is  it  well  to  wait  until  the  outlook  is  so 
desolate  ?  Is  lung  collapse  such  a  desperate  operation  as  to  be  used  only 
as  a  last  resort?"  Murphy  originally  advised  the  treatment  in  the 
earliest  stages,  as  well  as  in  the  advanced  ones.  When  a  patient  comes 
with  an  initial  hemorrhage  or  cough,  treat  him  as  you  would  a  tuber- 
culosis of  the  spine  or  any  other  joint — put  the  part  at  rest.  It  is 
exactly  the  appendix  proposition  over  again — namely,  that  the  phy- 
sician and  surgeon  are  waiting  for  the  disease  to  "ripen"  before  insti- 
tuting sufficient  measures  for  its  cure.  Years  ago,  in  medicine,  this 
procrastination  was  considered  an  evidence  of  genius  and  conserva- 
tism. It  is  really  a  stigma  of  ignorance,  timidity,  and  incompetency. 
"We  believe  this  method  most  practical  in  the  early  stage  of  apical 
and  monolobular  tuberculosis,  as  there  the  pathological  conditions  are 
such  that  compression  can  be  easily  accomplished  and  adhesions  are 
not  likely  to  be  found.  He  does  not  consider  that  it  is  indicated  or 
practical  in  far  advanced  or  chronic  cases,  where  the  fibrous  tissue 
deposited  will  not  permit  of  much  compression.  Theoretically  the  dan- 
gers of  compression  are:  (a)  Hemorrhage  from  wounding  intercostal 
vessels;  (b)  Injection  of  gas  into  an  intercostal  vein;  (c)  Infection  by 
impure  gas,  infected  trocar,  or  improper  antiseptic  preparation  of  the 
chest  waU;  (d)  Rupture  of  infected  foci  into  pleural  cavity  through 
compression  of  the  lung  and  separation  of  pleuritic  adhesions;  (e)  Dysp- 
nea from  too  large  quantities  of  gas;  (f)  Puncture  of  lung  with  needle; 
(g)  Pleural  reflexes  resulting  in  collapse,  spasm  of  the  larynx,  etc. 
Only  one  accident  has  ever  occurred,  one  case  reported  by  Lemke,  where 
the  patient  had  an  air-embolism  resulting  in  a  hemiplegia. 

The  quantity  of  gas  should  always  be  large,  as  much  as  will  be  tol- 
erated without  great  dyspnea;  this  quantity  can  always  be  injected 
without  a  great  plus  pressure.  If  compression  is  indicated  at  all,  real 
compression  is  indicated — 60,  150  or  200  cubic  inches  may  be  injected 
at  a  sitting,  if  properly  administered.  Many  men  inject  their  patients 
at  periods  of  from  six  weeks  to  six  months.  Our  experience  shows  con- 
clusively that  considerable  absorption  takes  place  in  three  to  four 
weeks,  and  that  three  to  six  weeks  is  the  time  to  elapse  between  injec- 
tions.   The  lung  must  be  kept  completely  collapsed.     All  authors  agree 


JOHN  B.   MURPHY,  M.D.,  AND  PHILIP  KREUSCHEB,  M.D,  25 

that  compression  must  be  kept  up  a  long  time.  Forlanini  says  it  must 
be  continued  indefinitely  in  an  advanced  phthisis  with  disseminated  or 
extensive  foci,  and  in  cases  in  which  the  other  lung  has  lesions  or  is 
threatened.  He  has  shown  that  a  properly  proportioned  pneumothorax 
of  one  side  does  not  injure  the  non-compressed  lung.  If  the  latter  is 
diseased  and  the  lesions  not  so  extensive  as  to  allow  compensatory  respi- 
ration for  the  compressed  lung,  Forlanini  claims  that  it  may  heal  or  be 
arrested  through  a  mechanism  not  easily  explained  but  which  is  com- 
pletely opposite  to  that  by  which  a  cure  is  affected  in  the  compressed 
lung.  Apical  lesions  are  not  as  dangerous  as  lesions  situated  centrally. 
The  lesions  may  in  rare  instances  be  aggravated  by  increased  functions 
or  by  the  amount  of  toxins  liberated,  so  that  treatment  may  have  to  be 
discontinued  for  a  time,  or  continued  cautiously. 

A  number  of  operative  accidents  during  and  after  introduction  of 
nitrogen  gas  have  been  reported.  From  our  experience  we  believe 
that  fatal  results  are  due  to  failures  in  technique  and  the  absence  of 
knowledge  of  accidents  that  can  occur  in  the  surgery  of  the  lungs,  inde- 
pendently of  pneumothorax  treatment.  It  is  suggested  that  men  who 
expect  to  follow  this  line  of  work  should  do  experiments  on  animals,  as 
this  will  give  a  knowledge  of  inestimable  value  in  therapeutic  work. 
Death  from  dyspnea  should  not  occur.  If  the  attending  surgeon  is  on 
the  alert,  all  that  he  needs  to  do  to  avoid  a  fatality  is  to  introduce  a 
trochar  or  a  large  aspirating  needle  into  the  pleura  on  the  side  of  the 
pneumothorax  and  permit  air  to  escape  and  thus  reduce  the  plus  pres- 
sure, or  he  can  freeze  the  skin  with  a  little  salt  and  ice,  cut  it,  then 
with  a  hemostat  spread  the  tissues,  rupture  the  pleura,  open  it  for  the 
air  to  escape  and  thus  save  the  patient.  We  had  but  a  single  rupture 
of  the  lung  or  bronchus  into  the  pleura.  The  absence  of  this  accident 
is  due  to  the  fact  that  our  apparatus  scarcely  has  a  plus  pressure,  as  it 
carries  only  %  oz.  to  a  square  inch. 

Balboni  gives  anatomical  proofs  of  recovery  through  cicatrization 
of  aU  destructive  lesions  of  the  lung  which  had  been  treated  with  arti- 
ficial pneumothorax.  Forlanini,  in  the  microscopic  study  of  three  cases, 
noticed  first  atelectasis;  second,  an  extraordinary  tendency  to  forma- 
tion of  hard  masses  about  the  bronchi  and  large  vessels  in  the  pneu- 
monic foci;  and  third,  the  formation  of  a  capsule  about  the  lesions  and 
a  tendency  to  cicatrization.  Graetz,  Brasche  and  Wurtzen  have  since 
confirmed  his  findings. 

Murphy  has  never  advocated  administering  the  gas  through  an 
incision.  Our  technique  is  as  follows:  The  patient  is  placed  in  a  com- 
fortable sitting  position.  If  the  apex  is  the  site  of  the  lesion,  the 
needle  is  to  be  inserted  in  the  fifth  or  sixth  interspace  between  the 
anterior  and  mid-axillary  line.  If  it  be  a  middle  or  lower  lobe  tuber- 
culosis, the  injection  should  be  made  over  the  upper  lobe,  in  the  fourth 
interspace,  just  outside  of  the  mammary  line.  Ethyl  chloride  or  novo- 
caine  may  be  used  for  local  anaesthesia.  A  tenotome  puncture  should 
always  be  made  through  the  skin,  to  permit  easy  insertion  of  the  needle 


26  PNEUMOTHORAX  AND  REST  TREATMENT 

and  to  prevent  the  introduction  of  septic  fragments  into  the  pleura. 
It  is  important,  after  the  needle  is  inserted  and  before  the  tube  is 
attached,  to  assure  oneself  that  the  point  of  the  needle  is  in  the  pleural 
cavity.  After  a  few  deep  inspirations,  if  a  little  air  has  entered  the 
pleural  cavity,  there  will  be  a  current  during  both  phases  of  respira- 
tion. The  opening  of  the  needle  should  be  covered  with  cotton  for  fil- 
tering the  air  that  is  admitted.  Sometimes,  even  though  the  point  of 
the  needle  be  within  the  pleural  cavity,  the  current  of  gas  meets  with 
considerable  resistance,  due  to  the  fact  that  unless  some  pressure  is 
used,  it  impinges  on  a  small  area  of  lung  tissue.  To  determine  that 
the  tip  of  the  needle  is  in  the  pleural  cavity,  a  manometer  is  used,  after 
the  manner  of  Gray.  We  always  use  a  blunt  needle,  aspirating  size,  with 
an  additional  opening  on  the  side  of  the  needle  near  its  tip.  This  per- 
mits the  gas  to  pass,  should  the  tip  be  plugged  with  tissue.  After  the 
needle  is  introduced,  it  is  attached  to  the  tubing  leading  to  the  cylin- 
der containing  nitrogen.  The  quantity  of  gas  varies  from  50  to  200 
cubic  inches.  The  amount  to  be  given  is  best  regulated  by  symptoms  of 
distress,  dyspnea  and  displacement  of  mediastinal  contents  and  dia- 
phragm. The  wound  is  sealed  with  collodion  and  a  small  firm  compress 
is  placed  over  the  puncture,  to  prevent  escape  of  gas  into  the  subcutan- 
eous tissue.  The  patient  is  placed  in  bed  in  a  comfortable  position.  If 
cough  or  dyspnea  are  annoying,  a  small  hypodermic  of  heroin  may  be 
given.  Skiagrams  should  be  made  before  and  after  injections,  to  watch 
the  extent  of  lung  collapse  and  note  the  pressure  on  the  heart  and  medi- 
astinum. 

Thousands  of  cases,  from  the  literature,  show  a  complete  symptomatic 
cure  and  many  vast  improvements  in  a  great  majority  of  patients.  From 
an  experience  of  nearly  500  cases,  with  an  aggregate  of  2,500  injections, 
by  Murphy  and  his  associates,  we  conclude  that  artificial  pneumothorax 
should  always  be  made  in  every  case  of  pulmonary  tuberculosis  where 
there  is  no  absolute  contra-indication. 

In  reviewing  the  results  obtained  in  our  own  cases  and  those  collected 
from  the  literature,  we  may  sum  up  the  following  advantages  of  pul- 
monary rest:  The  decline  or  disappearance  of  fever,  diminution  and 
disappearance  of  expectoration  with  partial  or  complete  disappearance 
of  the  bacilli,  gradual  increase  in  weight,  lessened  frequency  of  hem- 
orrhage, great  general  improvement  and  the  short  time  in  which  these 
changes  take  place. 

We  are  convinced  that  when  the  profession  as  a  whole  adopts  our 
original  plan  of  early  treatment,  the  percentage  of  cures  will  be 
increased  greatly,  that  the  period  of  convalescence  and  incapacity  will 
be  reduced  to  a  minimum,  that  accidents  in  administration  will  be  neg- 
ligible in  number.  We  take  pardonable  pride,  we  hope,  in  seeing  this 
method  universally  adopted  sixteen  years  after  it  was  first  advanced 
by  us  as  an  effective  treatment  in  pulmonary  tuberculosis.  This  work 
is  carried  on  in  Murphy's  clinic  by  Kreuscher  with  very  gratifying 
results  in  a  large  percentage  of  cases. 


THE  PRESENT  STATUS  OF  TUBERCULIN  THERAPY 

By  Louis  Hamman,  M.D. 
baltimore 

The  object  of  this  paper  is  to  provide  the  practicing  physician  with 
a  guide  to  tuberculin  treatment.  In  accord  with  this  object  I  must 
assume  that  the  reader  is  inexperienced  in  the  use  of  tuberculin,  and 
particularly  where  methods  are  concerned,  give  these  in  their  prac- 
tical detail  rather  than  in  principle.  There  is  a  widespread  interest  in 
the  treatment,  but  few  have  reviewed  critically  upon  what  evidence  its 
claims  to  serious  consideration  are  based.  Among  the  general  acclaim 
of  tuberculin  there  are  a  few  dissenting  voices  and  these  must  be 
heeded.  Before  studying  the  elaborate  principle  of  treatment  and  the 
methods  of  application,  one  naturally  wishes  to  know  the  results  that 
have  been  obtained.  It  is  from  this  angle  that  we  will  approach  tuber- 
culin treatment. 

Most  of  the  evidence,  upon  analysis,  is  reduced  to  impressions.  There 
are  inherent  difficulties  in  statistical  studies  of  tuberculosis  that  make 
it  arduous  to  seek  evidence  in  that  direction,  and  animal  experiments 
are  far  from  satisfactory.  Almost  always  the  treated  animal  lives  longer 
than  the  untreated,  but  tuberculin  has  never  stopped  or  even  limited 
an  established  infection.  It  is  common  to  read  in  literature  that  animals 
have  been  "immunized"  with  different  varieties  of  tuberculin.  Such 
statements  are  seldom  accompanied  by  detailed  protocols  and  do  not 
bear  close  scrutiny.  Real  immunity  or  resistance  to  tuberculous  infec- 
tions have  been  obtained  only  with  living  tubercle  bacilli.  While  it 
would  be  a  great  comfort  to  have  tuberculin  treatment  established 
firmly  upon  an  experimental  basis,  still  the  absence  of  conclusive  results 
in  animals  does  not  settle  the  question  of  its  value.  The  value  of  tuber- 
culin treatment  must  rest  ultimately  upon  the  clinical  results  of  its 
administration. 

Regardless  of  Koch's  injunction  that  tuberculin  was  to  be  used  in 
early  and  moderately  advanced  stages  of  pulmonary  tuberculosis,  the 
remedy,  after  its  introduction,  was  applied  recklessly  in  all  stages  of 
the  disease.  Large  doses  were  then  administered,  and  it  is  shocking  to 
glance  over  the  clinical  charts  preserved  from  those  days.  The  dis- 
appointment was  so  keen  and  the  memory  remaining  so  bitter  that  the 
weight  of  more  recent  conservative  work  has  failed  to  overbalance  the 
repugnance  left  in  the  minds  of  many  physicians.  Although  the  early 
tuberculin  era  ended  in  disaster,  still  the  results  obtained  even  then 
were  not  all  unfavorable.  Recently  a  prominent  clinician  has  written 
reminiscently  of  the  immediate  and  permanent  benefits  of  tuberculin 
treatment,  judged  after  a  sobering  interval  of  nineteen  years.  Many 
felt  that  the  downfall  of  tuberculin  was  occasioned  by  its  indiscriminate 
and  unreasonable  application,  and  that  perhaps  more  cautious  dosage 
would  avoid  the  dangers,  while  preserving  the  beneficial  effects.     Upon 


28 


THE  PRESENT  STATUS  OF   TUBERCULIN   THERAPY 


this  plan  many  continued  the  use  of  tuberculin,  convinced  that  they 
were  getting  good  results.  These  results  received  the  endorsement  of 
Koch,  and  from  the  time  of  their  publication  dates  the  modern  era  of 
tuberculin  treatment. 

All  statistical  studies  of  phthisis  are  surrounded  with  difficulties, 
and  these  are  well  nigh  insurmountable  in  a  statistical  study  of  methods 
of  treatment.  Standards  of  diagnosis  are  variable,  and  accurate  classi- 
fication for  purposes  of  comparison  is  almost  impossible.  The  difficulties 
of  classification  reside  chiefly  in  the  lack  of  correspondence  between  the 
extent  of  the  disease  and  the  severity  of  symptoms.  Until  the  past  few 
years.  Turban's  classification,  based  entirely  upon  the  extent  of  pul- 
monary involvement,  was  in  general  use.  More  recently  the  National 
Association  has  proposed  a  schema  which  takes  into  account  signs  and 
symptoms  which  have  been  universally  adopted.  Although  classification 
of  phthisis  is  inadequate,  an  estimate  of  the  results  of  treatment  are  still 
more  unsatisfactory.  More  satisfactory  standards  of  comparison  have 
recently  been  proposed,  as:  (1)  Working  ability;  (2)  disappearance  of 
tubercle  bacilli  from  the  sputum;  (3)  duration  of  life.  They  are 
arranged  in  inverse  order  of  their  importance. 

To  overcome  the  influence  of  spontaneous  variation  in  the  course  of 
the  disease  a  large  number  of  patients  should  be  studied.  Side  by  side 
with  the  tuberculin  treated  patients  an  equal  number  of  patients  as 
nearly  similar  as  possible,  should  be  observed  under  identical  conditions, 
save  that  tuberculin  is  withheld.  Many  statistical  studies  to  which  unde- 
served esteem  has  clung  dwindle  into  personal  impressions,  and  as  such 
they  retain  their  just  value. 

I  now  present  the  sputum  statistics.  They  speak  strongly  for  the 
healing  effect  of  tuberculin: 

Author  Open  Cases  Tuberculin  Treated 


Lost  Bacilli  in  the  Sputum 


Not  Treated  With  Tuberculin 
Lost  Bacilli  in  the  Sputum 


Kremer 


110 


Of  55  cases 41% 


Of  55  cases. 


.29% 


PhiUipi 


126 


II  stage. 
ni  stage. 


58% 
31% 


n  stage, 
m  stage. 


.19% 
.   7% 


Turban 


159 


86  eases 47% 


24  cases 27% 


Brown 


I  stage. 
n  stage. 


67% 
44% 


I  stage, 
n  stage. 


.64% 
.24% 


Baudelier  202  129  cases 64.9% 

12       I  stage 100% 

113  ni  stage....   50% 


Lowenstein 


682 


369  cases 53% 


Average  of  20  years' 
untreated  e  x  p  e  - 
rience  only 15% 


Baudelier  has  classified  his  500  cases  also  from  the  point  of  working  capacity. 

— Total —  Stage  I     Stage  H  Stage  III 

Cases   Per  Cent  Per  Cent  Per  Cent  Per  Cent 

Complete  earning  capacity  on  discharge.  . .  .   500         69.8  90.4         80.7         32.8 

Sputum  changed  from  positive  to  negative.  .    202         63.9         100  87.3         44.0 

It  is  seen  from  the  table  that  statistics  based  on  sputum  becoming 


LOUIS    HAMMAN,    M.D.  29 

negative  afford  a  real  evidence  of  improvement.  The  parallelism 
between  the  two  sets  of  figures  is  close. 

Favorable  reports  of  tuberculin  treatment  in  so-called  surgical 
cases  of  tuberculosis  are  no  less  numerous.  Tuberculous  larjmgitis  is 
a  thankful  field  for  this  method,  and  also  tuberculous  lesion  of  the 
eye.  In  serous  membrane  tuberculosis,  many  find  tuberculin  of  value. 
Most  surgeons  advise  post  operative  treatment,  with  tuberculin  in  renal 
tuberculosis.  Many  investigators  commend  tuberculin  in  tuberculous 
adenitis  upon  the  basis  of  excellent  results  observed  in  a  large  number 
of  cases.  From  the  consideration  of  this  evidence  the  following  con- 
clusions are  warranted.  Tuberculin  is  not  a  cure  for  tuberculosis,  else 
such  a  detailed  consideration  were  unnecessary.  However,  in  many 
instances  it  produces  healing,  and  recovery  is  more  certain  and  more 
lasting  than  without  it.  Such  a  conservative  estimate  of  its  influence 
ranks  tuberculin  as  a  favorable  factor  in  the  management  of  the  dis- 
ease, a  favorable  factor  as  rest  and  diet  are  favorable  factors.  This 
being  its  position,  it  behooves  us  to  give  it  wide  application,  but  not 
to  the  exclusion  of  other  favorable  factors,  but  in  combination  with 
these. 

All  tuberculin  may  be  divided  into  three  groups:  (1)  Those  pre- 
pared from  the  culture  media  in  which  tubercle  bacilli  have  grown; 
(2)  those  prepared  from  the  bacilli  themselves;  (3)  those  prepared  by 
various  methods  of  extracting  the  tubercle  bacilli.  The  principal  mem- 
bers of  group  (1)  are:  Koch's  Original  or  Old  Tuberculin,  O.T. ;  Denys' 
Bouillon  Filtrate,  B.F. ;  Jochmann's  Albumose  Free  Tuberculin,  A.F. ; 
Koch's  Bacillen  Emulsion,  B.E. ;  Koch's  Tuberculin  Residue  or  New 
Tuberculin,  T.R. ;  Beraneck's  Tuberculin;  Von  Ruck's  Watery  Extract; 
Landman's  Tuberculol.  It  mil  be  seen  from  this  list  that  there  has 
been  a  feverish  strife  to  improve  Old  Tuberculin.  Two  considerations 
prompted  these  efforts:  (1)  To  attempt,  under  the  assumption  that  they 
are  many,  to  include  all  the  potent  portions  of  the  tubercle  bacillus  in 
the  preparation;  (2)  to  attempt  to  remove  supposed  deleterious  sub- 
stances from  the  culture  media  of  the  bacilli  themselves,  while  pre- 
serving the  beneficial  or  immunizing  substances.  We  know  too  little 
about  the  constitution  of  tuberculin  to  identify  it  by  any  chemical  test. 
There  is  only  one  characteristic  of  tuberculin  that  is  absolutely  specific — 
namely,  the  power  to  produce  certain  reactions  in  tuberculous  animals. 
Briefly,  the  features  of  this  reaction  are  redness  and  swelling  at  the 
point  of  injection,  inflammatory  reaction  about  the  lesion,  and  fever 
and  constitutional  symptoms.  Recent  investigations  show  conclusively 
that  the  potent  substance  in  tuberculin  that  causes  the  reaction  is  the 
protein  of  the  bacillus.  A  product  containing  this  protein  is  a  tuber- 
culin, and  no  substance  that  does  not  contain  it  can  be  so  classified. 

There  is  no  other  characteristic  mark  of  tuberculin.  That  settles 
at  once  all  discussion  about  the  value  of  many  different  tuberculins. 
All  are   satisfactory   if   they    contain   the  protein  and  the  test  of  the 


30  THE  PRESENT  STATUS  OF   TUBERCULIN  THERAPY 

presence  of  these  proteins  is  their  ability  to  produce  the  tuberculin 
reaction. 

Different  strains  of  tubercle  bacilli  produce  widely  different  tuber- 
culin. The  variation  is  in  strength  alone,  the  character  of  their  effects 
being  invariably  the  same.  Romer,  after  extensive  investigations  of 
effects  of  tuberculin  from  human,  bovine  and  fowl  tubercle  bacilli  upon 
animals  (guinea  pigs,  cattle,  chickens  and  rabbits)  infected  with  human, 
bovine  and  fowl  bacilli,  concludes  that  there  is  no  essential  difference 
in  the  character  of  effects  they  produce.  Indeed,  human  and  bovine 
tuberculins  are  so  identical  in  their  action  upon  infected  animals  that 
we  may  neglect  to  ascertain  their  source.  Practically  all  tuberculins  are 
efficient.  Tuberculin  acts  by  stimulating  the  patient  to  elaborate  pro- 
tective substances,  or  to  an  inflammatory  reaction  about  the  area  of 
infection.  The  most  suitable  patients  for  treatment  are  those  with  small 
localized  lesions  that  are  not  producing  constitutional  symptoms — 
namely,  pulmonary  tuberculosis,  tuberculosis  of  the  glands,  bones,  eye, 
etc.  Many  patients  have  reaped  a  measure  of  improvement  from 
hygienic  dietic  treatment,  but  then  for  months  remained  stationary. 
Tuberculin  is  often  just  the  stimulation  they  need  to  start  them  upon 
a  course  of  rapid  improvement.  Entirely  unsuited  for  tuberculin 
treatment  are  patients  exhausted  by  the  disease  or  with  actively  pro- 
gressing infection.  Advanced  cases  with  fever  and  emaciation  and 
those  with  acute  disseminated  tuberculosis  are  to  be  excluded.  Between 
the  groups  definitely  suitable  and  definitely  unsuitable  for  treatment 
is  the  large  class  of  border-line  cases.  In  many  of  these,  when  tuber- 
culin is  cautiously  given,  it  does  no  harm ;  and  in  many  cases  it  must  be 
started  tentatively  with  a  readiness  to  discontinue  or  push  on  according 
to  the  result  obtained.  When  patients  with  fever  fail  to  respond  to  pro- 
longed rest  in  bed,  in  my  experience,  they  usually  fail  to  respond  to 
tuberculin. 

Although  there  are  innumerable  variations  in  the  administration  of 
tuberculin  these  methods  can  be  reduced  to  two:  (1)  Giving  small 
doses  and  repeating  the  same  small  dose  at  stated  intervals;  (2)  start- 
ing with  small  doses  and  progressively  increasing  the  dose,  varying  the 
time,  interval  and  rate  of  progression  to  suit  individual  conditions.  One 
plan,  advocated  by  Lowenstein,  is  to  reach  high  doses  of  tu-berculin  in  the 
shortest  time  possible.  Another  plan,  represented  by  Trudeau,  Sahli  and 
Denys,  aims  to  arrive  at  as  high  grade  of  tuberculin  tolerance  as  possible, 
but  the  reaching  of  high  doses  is  not  the  ultimate  object.  I  agree  with  Sahli 
that  we  succeed  in  reaching  as  high  doses  by  the  mild  plan  as  by  the  more 
daring  plan,  that  the  improvement  is  equally  satisfactory,  and  that  less 
danger  is  run.  Briefly,  the  best  method  of  using  tuberculin  is  to  give 
increasing  doses  with  the  purpose  of  producing  the  greatest  amount  of 
focal  stimulation  without  liberating  general  reaction. 

For  practical  purposes  we  find  the  simplest  method  is  to  prepare  a 
series  of  dilutions,  each  being  one-tenth  the  strength  of  the  former. 


LOUIS   HAMMAN,    M.D.  31 

Bottle  No.  I  contains  pure  tuberculin;  No.  II,  9  c.c.  diluent  and  1  c.c. 
tuberculin ;  No.  Ill,  9  c.c.  diluent  and  1  c.c.  of  II ;  No.  IV,  9  c.c.  diluent 
and  1  c.c.  of  III,  etc.  The  diluent  is  0.8  per  cent,  salt  solution  with 
0.25  per  cent,  carbolic  acid.  To  give  1  c.mm.,  give  0.1  c.c.  of  bottle  III, 
5  c.mm.  0.5  c.c.  of  III,  etc.  The  dilutions  should  be  kept  in  a  cool 
dark  place,  when  not  in  use.  Fresh  dilutions  should  be  made  every 
two  weeks;  we  note  no  change  in  strength  in  this  period.  To  make 
the  dilutions  one  needs  a  flask  for  the  sterile  salt-carbolic  solution,  a 
number  of  wide-mouthed  glass-stoppered  bottles  and  two  pipettes,  one 
with  a  relatively  large  bore  accommodating  10  c.c.  and  graduated  in 
tenths  of  a  c.c,  one  with  a  fine  bore  accommodating  0.1  c.c,  and  grad- 
uated in  hundredths  of  a  c.c. 

The  injections  are  made  subcutaneously,  so  when  local  reaction  occurs 
it  can  be  readily  detected.  The  syringe  and  needle  should,  of  course, 
be  boiled  before  use,  and  care  be  taken  that  tuberculin  solutions  remain 
sterile.  The  skin  needs  only  to  be  rubbed  with  alcohol.  Other  routes 
of  administration  have  been  proposed.  Intravenous  injections  first  made 
by  Koch  run  danger  of  severe  reactions.  The  oral  route  was  recom- 
mended by  Freymuth;  its  effects  are  uncertain.  Other  methods  not  in 
general  use  are  by  inhalation  and  intrabronchially,  cutaneously,  and 
directly  to  cutaneous  tuberculous  lesions. 

My  experience  has  been  mainly  with  B.  F.  and  0.  T.  For  B.  F., 
I  consider  0.0001  c.mm.  the  dose  generally  suitable  for  beginning  treat- 
ment. For  0.  T.,  0.001.  For  T.  R.  and  B.  E.,  0.001  to  0.005  c.mm. 
T.  R.  contains  10  mg.  and  B.  E.  5  mg.  of  ground  bacilli  in  each  c.c. 
It  will  be  seen  that  the  initial  dose  of  all  tuberculins  is  in  the  neighbor- 
hood of  0.001  c.mm.  Severe  reactions  never  occur  after  this  dose,  and 
mild  reactions  can  do  no  harm.  .  .  .  When  shall  the  second  dose  be 
given?  The  empirical  results  of  clinicians  have  made  the  selection  of 
from  three  to  five  days  almost  universal.  Our  routine  at  Johns  Hopkins 
Hospital  is  to  administer  small  doses  twice  a  week  until  we  have  reached 
the  level  of  the  patient's  tolerance,  when  we  change  to  the  week  interval. 
If  the  patient  shows  no  evidence  of  intolerance  we  change  to  the  week 
interval  when  10  c.mm.  is  reached.  Our  aim  is  the  greatest  amount  of 
focal  stimulation  without  liberating  general  reactions.  The  symptoms 
of  tuberculin  reaction  are:     (1)  The  general  constitutional  symptoms; 

(2)  the  focal  reactions  or  changes  occurring  about  the  diseased  area; 

(3)  the  localized  reaction  occurring  at  the  point  of  injection.  The 
elevation  of  a  few  fifths  of  a  degree  above  the  usual  maximum  tempera- 
ture should  receive  careful  consideration  and  the  relation  to  the  injection 
should  be  studied.  If  the  temperature  has  been  constantly  subnormal 
with  wide  daily  variations  in  range,  under  treatment  the  mean  level 
may  rise  gradually  toward  normal  and  the  oscillations  become  smaller. 
Such  an  occurrence  must  be  viewed  as  a  favorable  effect  of  the  treat- 
ment. Temperature  rise  occurring  during  tuberculin  treatment  and 
not  due  to  the  injections  may  be  grouped  in  three  classes:    (1)  Due  to 


32  THE  PRESENT  STATUS  OF  TUBERCULIN   THERAPY 

external  influence,  over-exertion,  fright,  emotion,  an  unexpected  visit, 
animated  conversation  or  excitement,  as  over  a  game  of  cards.  (2)  All 
patients  with  tubercidosis  are  susceptible  to  variations  in  temperature 
that  are  not  easily  explained  and  these  are  interpreted  as  evidences  of 
auto-inoculation.  On  account  of  changes,  probably  in  circulatory,  about 
the  lesion,  absorption  is  suddenly  increased  and  the  patient  has  endo- 
genous tuberculin  reaction.  (3)  Inter-current  infections  are  a  fertile 
source  of  temperature  elevation.  Loss  of  weight  as  an  isolated  symptom 
is  sometimes  the  first  warning  of  intolerance.  It  is  valuable  as  a  sign 
of  overdosage  late  in  the  treatment.  The  focal  reaction  is  of  some  value 
in  guiding  dosage  when  the  lesion  is  situated  externally.  I  regard  the 
appearance  of  fresh  rales  as  the  only  reliable  mark  of  pulmonary  focal 
reaction.  Local  reaction  is  the  most  valuable  of  the  three  in  calling 
our  attention  to  the  proximity  of  the  border-line  tolerance.  Local 
reactions  must  be  looked  for  carefully,  and  the  site  of  the  previous 
injection  always  inspected  before  the  following  dose  is  administered. 
All  regions  of  the  body  are  not  equally  sensitive  to  tuberculin.  Local 
reactions  occur  much  earlier  when  injections  are  made  in  the  arm  than 
when  the  back  is  selected.  For  this  reason  we  prefer  the  subcutaneous 
tissue  of  the  back. 

During  the  preliminary  period  of  small  dosage  it  is  safe  and  advisable 
to  double  the  amount  of  each  injection  until  symptoms  warn  that  the 
level  of  tolerance  has  been  reached,  or  if  these  do  not  appear  until 
0.1  c.mm.  is  reached.  Reactions  occur  more  commonly  to  doses  from 
0.1  to  10  c.mm.  than  at  any  other  level.  It  is  the  period  that  requires 
the  greatest  vigilance,  for  when  10  c.mm.  is  passed,  progress  from  then 
is  usually  unobstructed.  When  0.1  c.mm.  is  reached,  the  dose  may  be 
increased  by  tenths.  Thus  we  would  give  0.1,  0.15,  0.25,  0.3,  0.4,  0.5, 
0.7,  1.0,  etc.    This  plan  is  simple,  and  in  practice  works  well. 

If  symptoms  of  reaction  appear  in  the  absence  of  a  general  reaction, 
the  further  course  will  depend  entirely  upon  the  patient.  (1)  In  a 
number,  by  slowly  and  cautiously  increasing  the  dose,  this  early  period 
of  hypersensitiveness  is  soon  overcome  and  thereafter  we  can  rapidly 
increase  the  dose.  (2)  The  patient's  sensitiveness  may  remain  at  a 
remarkably  constant  level,  so  that  any  effort  to  go  beyond  a  certain 
dose  is  invariably  followed  by  a  general  reaction.  Such  constant  hyper- 
sensitiveness may  persist  for  years.  (3)  There  are  patients  who  per- 
sistently remain  at  a  given  level,  but  under  prolonged  treatment  grad- 
ually acquire  a  lower  hypersensitiveness,  and  the  doses  may  be  gradually 
increased.  Such  changes  are  marked  by  general  improvement  in  the 
patient's  condition. 

There  is  no  absolute  terminal  dose.  Most  observers  cease  raising 
the  dose  when  1,000  c.mm.  is  reached.  Often  this  dose  is  exceeded. 
When  this  maximum  is  reached  some  physicians  advise  repeating  it 
indefinitely  at  10  to  14-day  intervals;  others  advise  breaking  off  the 
treatment  temporarily.     If  it  is  decided  to  give  a  second  course  of 


LOUIS  HAMMAN,   M.D.  33 

tuberculin,  treatment  may  be  pushed  more  vigorously.  A  course  of 
treatment  extending  over  a  period  of  six  to  twelve  months  does  not  cure 
tuberculosis.  Often  the  symptoms  completely  disappear,  though  the 
lesion  persists.  In  others  the  lesion  may  apparently  be  healed,  but  we 
fear  a  fresh  outbreak.  Most  clinicians  are  in  favor  of  repeated  courses 
of  treatment.  Tuberculin  tolerance  developed  under  treatment  persists 
for  a  long  time,  often  unabated  for  a  year.  Therefore  treatment  may 
be  begun  at  higher  doses  and  rapidly  increased. 


X-RAY  DIAGNOSIS  OF  TUBERCULOSIS  OF  THE  LUNGS 
AND  BRONCHIAL  GLANDS 

(Abstract) 
By  Hollis  E.  Potter,  M.D. 

CHICAGO 

1.  Radiography  is  not  a  competitor  of  other  clinical  methods,  but 
an  additional  means  of  diagnosing  lung  tuberculosis. 

2.  In  certain  cases  a  positive  diagnosis  by  X-rays  is  possible,  where 
the  best  of  clinicians  can  only  write  "suspected."  The  reason  for  this 
is  that  the  signs  and  symptoms  do  not  always  run  parallel  with  the 
pathology.    The  X-ray  procedures  are  aimed  directly  at  the  pathology. 

3.  Certain  other  cases  give  presumptive  signs  and  symptoms,  with 
no  positive  X-ray  findings.  In  a  long  series  of  cases  the  clinical  and 
X-ray  findings  are  found  to  agree  in  the  main. 

4.  The  tubercular  invasion  is  demonstrable  by  Roentgen  rays  on 
account  of  the  increased  density  of  the  tubercle  and  its  collateral  inflam- 
matory process  as  against  the  transparent  air-filled  areas  of  normal 
lungs. 

5.  Fluoroscopy  and  radiography,  especially  stereoscopic  radiography, 
both  have  their  advantages  in  the  X-ray  examination.  By  fluoroscopy 
one  easily  sees  the  gross  lesions,  the  diaphragmatic  movements  and  the 
degree  of  expansion  of  the  several  lobes  individually.  By  critical  radi- 
ography one  may  demonstrate  the  finest  granular  deposits  not  easily  seen 
fluoroscopically.     A  thoroughgoing  examination  includes  both  methods. 

6.  The  early  radiologic  signs  of  pulmonary  tuberculosis  are: 

(a)  Lessened  diaphragmatic  excursion  on  the  affected  side. 

(b)  Failure  of  the  affected  lung  or  lobe  to  "light  up"  during  deep 
inspiration. 

(c)  Positive  demonstration  of  pulmonary  infiltrations  of  the  type 
usually  associated  with  tuberculosis.  In  early  cases  these  deposits  may 
appear  like  the  shadow  of  dried  leaves  on  a  branch,  like  grapes  in  a 
cluster  or  as  discrete  unconnected  masses  with  a  granular  or  flocculent 
appearance. 

(d)  Later  cases  are  also  variable  in  their  appearance,  showing  larger 
masses  and  perhaps  large  areas  of  consolidated  lung. 

7.  Healed  lesions  are  on  the  whole  more  discrete  than  active  ones, 
being  composed  of  denser,  more  homogeneous,  retracted  tissue.  In  many 
cases  the  activity  of  the  process  can  be  estimated. 

8.  Valuable  evidence  is  usually  obtained  regarding  cavity,  pleural 
effusions,  pleural  thickening,  pneumothorax,  tubercular  pneumonia,  etc. 

9.  The  differential  diagnosis  between  tubercular  shadows  and  those 
seen  in  bronchiectasis,  and  certain  cases  of  broncho-pneumonia,  blasto- 
mycosis, and  actinomycosis,  is  sometimes  difficult. 

10.     Bronchial  gland  tuberculosis  is  more   difficult  to  interpret  on 

84 


X-RAT   DIAGNOSIS   OF   TUBERCULOSIS  35 

accoTint  of  the  normal  existence  of  a  pronounced  hilus  shadow  and  the 
frequent  occurrence  of  non-tubercular  enlargements  of  the  hilus  glands 
by  anthracosis,  etc. 

Increased  hilus  shadows  have  more  diagnostic  importance  in  children 
than  in  adults  and  are  especially  important  if  associated  with  definite 
pulmonary  infiltrations  at  a  distance  from  the  hilus. 

DISCUSSION 

Frances  C.  Turley,  M.D.,  CMcago:  The  preceding  speaker  has  so 
thoroughly  and  competently  covered  the  subject  of  the  Roentgenolog- 
ical examination  of  the  lungs  and  bronchial  glands  for  tuberculosis 
that  but  little  is  left  to  be  said,  except  a  few  facts  in  confirmation  of 
the  statements  already  made. 

Undoubtedly  a  combination  of  the  two  methods,  fluoroscopy  and  the 
Eoentgenograms,  gives  the  best  results: — fluoroscopy,  for  the  observa- 
tion of  the  thoracic  walls  and  their  contents  in  motion,  for  locating 
gross  lesions  and  differentiating  fluids  from  lung  consolidations ;  and  the 
Roentgenogram,  because  it  is  considered  by  many  of  the  best  Roent- 
genologists as  an  absolute  necessity  for  the  detection  of  the  early 
lesions  of  incipient  and  doubtful  cases.  It  may  be  said  in  view  of  this 
opinion  that  no  case  should  be  dismissed  from  an  institution  as  cured 
until  a  thorough  search  has  been  made  with  the  X-ray  for  an  active 
lesion. 

Fluoroscopy  is  less  expensive  than  radiography  and  may  thus  prove 
very  valuable  for  the  observation  of  the  progress  of  cases  diagnosed 
but  under  treatment. 

It  is  a  fact  that  the  X-ray  will  show  in  a  Roentgenogram  more 
clearly  the  extent  and  the  character  of  the  involvement  of  a  tubercu- 
lous lung,  in  some  cases,  than  can  be  determined  by  the  most  careful 
physical  examination.  It  is  also  a  fact  that  the  lungs  may  be  exten- 
sively involved  in  a  tuberculous  process  and  no  tubercle  bacilli  be 
found  in  the  sputum,  though  present  in  the  air  vesicles.  In  such  cases 
there  is  no  doubt  about  the  value  of  the  Roentgenogram  because  such 
lesions  show  definitely  tuberculous,  in  almost,  if  not  quite,  all  cases. 

At  times  the  question  of  pulmonary  tuberculosis  is  brought  to  the 
attention  of  the  physician  when  a  thorax  is  examined  for  other  lesions, 
on  account  of  the  striking  picture  presented  to  the  eye,  when  such  a 
condition  had  not  been  previously  under  consideration  as  a  cause  of  the 
symptoms. 

While  the  following  opinion  may  not  pass  unchallenged,  yet  it  is 
worthy  of  consideration,  namely,  nitrogen  gas  should  not  be  used  to 
collapse  a  lung  until  the  chest  of  the  patient  has  been  subjected  to  a 
recent  careful  Roentgen  examination  in  order  to  determine  the  relative 
condition  of  the  two  lungs,  and  as  far  as  possible  the  condition  of  the 
pleura,  and  the  number  and  location  of  pleural  adhesions,  if  any,  on 
the  side  chosen  for  operation.     In  conclusion  the  suggestion  might  be 


36  X-RAY  DIAGNOSIS  OF  TUBERCULOSIS 

made  that  the  operation  be  carried  out  under  fluoroscopic  observation 
if  it  were  not  that  such  observation  requires  total  darkness.  However, 
a  safe  technique  might  be  developed. 

James  T.  Case,  M.D.,  Battle  Creek,  Michigan:  In  incipient  tuber- 
culosis the  writer  holds  that  the  Roentgen  evidence  is  of  the  greatest 
value;  not  in  itself  alone,  but  in  conjunction  with  the  other  findings 
of  clinical  research.  This  is  true  of  the  X-ray  findings  in  any  disease. 
It  is  recognized  that  sometimes  the  X-ray  evidences  are  so  concrete 
one  may  say  at  once  that  the  condition  is  thus  and  so,  making  a  definite 
diagnosis.  But  even  in  these  cases,  for  the  sake  of  scientific  complete- 
ness and  accuracy,  the  X-ray  findings  should  be  carefully  correlated 
with  the  results  of  other  methods  of  research. 

So  it  is  also  in  pulmonary  tuberculosis.  In  the  very  early  stages, 
when  there  are  as  yet  only  catarrhal  changes  such  as  only  the  most 
expert  can  detect  by  ear  or  touch,  it  is  likely  that  the  X-ray  findings 
will  not  be  decisive.  The  most  one  may  be  able  to  say  is  that  there  is 
evidence  of  a  pulmonary  infection,  the  exact  nature  of  the  infecting 
agent  not  being  recognizable  from  the  X-ray  examination. 

When,  however,  caseation  has  supervened — and  this  is  fortunately 
a  comparatively  early  development — the  X-ray  findings  are  at  once 
decisive  as  to  the  extent  and  location  of  a  pulmonary  infection  which 
is  in  all  probability  tuberculous,  though  again  one  may  not  be  able  to 
place  himself  defiidtely  on  record  that  the  infecting  agent  is  Koch's 
bacillus.  The  geographical  disposition  of  the  signs  of  resistance  to 
infection,  and  still  later  perhaps  the  signs  of  defeat  in  the  face  of  infec- 
tion, in  pulmonary  tuberculosis,  are  often  so  characteristic  that  one  may 
say  definitely  that  the  lesion  is  tuberculosis. 

In  more  advanced  stages  of  the  disease,  the  X-ray  examination  is 
less  essential  as  a  diagnostic  agent,  but  it  becomes  more  and  more  a 
confirmatory  means,  especially  in  helping  to  map  out  the  extent  of  a 
frank  lesion  or  in  estimating  the  virulence  of  the  process  in  the  various 
foci  of  infection.  Of  especial  value  is  the  X-ray  examination  when  the 
infection  is  central,  or  masked  by  emphysema  and  other  pulmonary  non- 
tuberculous  lesions.  The  Roentgen  findings  are  of  notable  value  in  the 
study  of  pleural  thickenings,  pleural  effusions  and  exudates,  and  espe- 
cially in  inter-lobar  affairs. 

Pulmonary  malignancies  may  usually  be  differentiated  by  the  Roent- 
gen findings,  especially  when  there  are  signs  elsewhere  indicating  the 
site  of  the  primary  lesion. 

The  technic  is  of  the  greatest  importance.  Fluoroscopic  examination, 
so  essential  in  gastro-intestinal  work,  is  here  of  relatively  small  value, 
at  least  in  the  incipient  stage  where  the  aid  of  the  X-ray  is  most  needed. 
Nevertheless  the  screen  study  is  essential  in  all  cases  for  the  proper 
estimation  of  the  action  of  the  diaphragm;  the  extent  of  interference 
due  to  adhesions  of  the  diaphragm  and  pericardium ;  the  degree  to  which 
certain  involved  areas  light  up  on  comparison  of  inspiration  and  expira- 


X-RAY   DIAGNOSIS   OF   TUBERCULOSIS  37 

tion;  the  determination  of  small  amounts  of  fluid  in  cavities  and  in  the 
costo-phrenic  angles. 

The  ordinary  single  Roentgenogram  is  not  of  much  value  in  exact 
studies,  but  the  stereoroentgenogram  is  of  the  greatest  possible  value. 
It  is  sometimes  necessary  to  make  stereoroentgenograms  both  anteriorly 
and  posteriorly,  but  the  anterior  stereoscopic  pair  is  ample  except  in 
very  important  cases  where  it  is  absolutely  essential  that  the  Roent- 
genolist  make  a  definite  statement  as  to  the  presence  or  absence  of  a 
pulmonary  lesion. 

The  speaker  has  found  of  highest  advantage  close  association  with  a 
splendid  physical  diagnostician  to  whose  accuracy  and  painstaking 
exactness  he  wishes  to  testify.  By  thus  combining  and  correlating  the 
results  of  physical  and  Roentgen  research,  the  abilities  of  both  clinician 
and  Roentgenologist  are  sharpened  to  the  utmost,  and  there  is  promise 
of  much  progress  in  the  near  future. 


EELATIVE    IMPORTANCE    OF    BOVINE    AND    HUMAN 
SOURCES  OF  INFECTION  IN  THE  PRODUC- 
TION   OF    TUBERCULOSIS 

By  M-  P-  Eavenel,  M.D. 
columbia,  mo. 

I  do  not  need  to  say  that  it  gives  me  a  great  deal  of  pleasure  to  be 
here  with  the  Eobert  Koch  Society  and  to  speak  to  you  on  this  occasion. 

Dr.  Sachs  asked  me  to  speak  on  this  subject — Bovine  Tuberculosis — 
which  has  been  a  special  study  of  mine  for  a  number  of  years. 

I  remember  very  well  that  Dr.  Welch  of  Johns  Hopkins  asked  me 
in  1912:  "Do  you  not  think  that  the  time  has  come  when  we  can  stop 
discussing  this  question  of  the  relation  between  bovine  and  human 
tuberculosis,  at  least  to  the  extent  of  not  making  it  a  prominent  subject 
in  our  meetings?"  I  told  him  that  I  felt  to  a  certain  extent  that  this 
could  be  done,  and  yet  the  question  crops  up  year  after  year.  Not  a 
legislature  meets  in  any  state  of  the  Union  that  the  question  does  not 
come  up  in  one  form  or  another.  We  are  constantly  confronted  with 
the  "cow  question,"  as  Dr.  Favill  has  called  it,  and  I  could  spend  very 
much  more  time  than  you  would  care  to  listen,  in  talking  on  bovine 
tuberculosis  as  an  economic  scourge,  as  a  farmers'  question,  a  "cow 
question,"  and  the  cost  to  us,  to  the  United  States,  and  to  the  world 
in  general,  and  also,  I  believe,  a  factor  in  the  high  price  of  living  at  the 
present  time.  However,  those  present  are  interested  in  it  chiefly  on 
account  of  its  relation  to  public  health,  and  on  that  phase  of  the  question 
I  am  going  to  spend  all  my  time  today. 

The  history  of  this  controversy  dates  back  to  1901,  at  the  British 
Congress  on  Tuberculosis.  Before  that  time  we  were  practically  a  unit 
in  believing  that  tuberculosis  was  the  same  in  whatever  animal  seen 
and  in  whatever  form  in  any  animal.  This  was  the  belief  of  Villemin, 
who  in  1865  first  showed  that  tuberculosis  was  a  communicable  disease. 
Koch  said  that  Villemin  did  thorough  and  methodical  inoculation 
experiments,  using  material  from  man  and  cattle,  "and  proved  experi- 
mentally the  identity  of  the  latter  disease  with  human  tuberculosis." 
As  a  result  of  his  own  experiments  Koch  says:  "The  perfect  identity 
and  unity  of  the  tuberculous  process  in  different  kinds  of  animals  can- 
not be  doubted." 

Koch  also  stated,  in  his  first  papers:  "It  seemed  to  me,  however, 
not  improbable  that  though  bacilli  from  various  forms  of  tuberculosis, 
perlsucht,  lupus,  phthisis,  etc.,  presented  no  differences  microscopically, 
yet  that  in  cultures,  differences  might  become  apparent  between  bacilli 
from  different  sources.  But  although  I  devoted  the  greatest  attention 
to  this  point,  I  could  find  nothing  of  the  kind.  I  was  not  able  to  demon- 
strate any  differences  in  the  effect  of  inoculation  with  material  derived 
from   varieties   of    the   tuberculous   process,    as   miliary   tuberculosis, 

38 


M.    P.    RAVENEL,   M.D.  39 

phthisis,  scrofula,  fungus,  inflammation  of  joints,  lupus,  perlsucht  and 
other  forms  of  animal  tuberculosis." 

The  whole  world  believed  until  1901  that  the  different  forms  of 
tuberculosis  were  the  same,  except  that  in  1896  Dr.  Theobald  Smith 
pointed  out  certain  differences  between  cultures  of  human  bacilli  and 
bovine  bacilli.     This  work  was  extended  and  enlarged  upon  in  1898. 

The  chief  differences  which  Dr.  Smith  observed  were  as  follows: 
(1)  The  human  bacillus  is  very  much  easier  to  grow  on  artificial  culture 
media  than  the  bovine.  (2)  The  human  bacillus  is  long,  slender  and 
stains  unevenly,  whereas  the  bovine  bacillus  is  short,  thicker,  and  stains 
evenly,  not  showing  vacuoles.  (3)  Most  important  of  all,  the  bovine 
bacillus,  for  all  experimental  animals,  shows  a  virulence  very  much 
greater  than  that  of  the  human. 

The  general  belief  until  1901  was  that  bovine  and  human  tuberculosis 
were  the  same  and  that  the  bovine  disease  could  be  transmitted  to  human 
beings.  At  the  British  Congress  on  Tuberculosis,  Koch  made  the  follow- 
ing statements: 

1.  Human  tuberculosis  differs  from  bovine  and  cannot  be  trans- 
mitted to  cattle. 

2.  Though  the  important  question,  whether  man  is  susceptible  to 
bovine  tuberculosis  at  all,  is  not  yet  absolutely  decided  and  will  not 
admit  of  absolute  decision  today  or  tomorrow,  one  is,  nevertheless, 
already  at  liberty  to  say  that  if  such  a  susceptibility  really  exists  the 
infection  of  human  beings  is  but  a  very  rare  occurrence.  I  should 
estimate  the  extent  of  infection  by  the  milk  and  flesh  of  tuberculous 
cattle  and  the  butter  made  of  this  milk  as  hardly  greater  than  that  of 
hereditary  transmission,  and,  therefore,  do  not  deem  it  advisable  to  take 
any  measures  against  it. 

In  regard  to  the  first  of  these  statements  it  has  been  repeatedly 
shown  that  cattle  can  be  infected  with  human  bacilli.  In  regard  to 
the  second  statement  and  the  comparison  to  hereditary  transmission, 
it  may  be  stated  that  tuberculosis  is  not  an  hereditary  disease.  The 
literature  of  all  the  world  shows  only  about  twenty-five  cases  of  true 
hereditary  tuberculosis;  even  in  animals  it  is  rare.  The  possibility  of 
hereditary  tuberculosis  is  recognized  as  an  academic  fact  but  practi- 
cally it  plays  no  part  in  the  spread  of  the  disease.  Koch's  statement 
was  equivalent  to  saying  that  there  was  no  danger  from  bovine  tuber- 
culosis. 

Koch's  opinions  raised  a  storm  of  opposition.  He  was  the  greatest 
authority  in  the  world  on  tuberculosis  and  such  an  opinion,  if  true, 
would  have  upset  not  only  aU  of  our  ideas,  but  the  laws  which  almost 
all  civilized  nations  had  enacted  to  protect  human  beings  against  the 
bovine  disease.  The  English  Government  soon  appointed  a  Royal  Com- 
mission, and  the  German  Government  an  Imperial  Commission.  The 
latter  was  presided  over  by  twenty-five  of  the  leading  professors  of 
the  German  Empire,  including  Koch  himself. 


40  SOURCES   OP  INFECTION  EN"   TUBERCULOSIS 

The  English  Commission  examined  108  cases,  of  which  84  showed 
human  infection,  19  bovine,  and  5  both  human  and  bovine.  In  other 
words,  22  per  cent  of  all  their  cases  showed  bovine  infection.  If  we 
analyze  these  cases  as  to  the  location  of  the  disease,  we  find  that  there 
were  38  cases  of  cervical  gland  and  abdominal  tuberculosis.  Of  these 
17  were  bovine,  19  human,  and  2  both  human  and  bovine.  Taking 
those  showing  abdominal  tuberculosis  alone,  there  were  29  cases,  14 
of  which  were  bovine,  13  human,  and  2  both  human  and  bovine. 

The  German  Commission  reported  that  of  84  children  examined  by 
them,  21,  or  25  per  cent,  had  derived  their  infection  from  bovine  sources. 
Against  this  laboratory  work  the  German  Commission  reports  a  col- 
lective investigation  done,  I  beHeve,  mostly  by  correspondence.  Six 
hundred  and  twenty-eight  persons  who  are  said  to  have  been  in  the 
habit  of  drinking  milk  from  tuberculous  cows  were  examined.  One 
group  containing  360  persons,  among  whom  were  151  children,  drank 
the  milk  uncooked.  Clinical  examination  showed  only  2  cases  of  tuber- 
culous adenitis  and  14  cases  of  suspected  tuberculosis.  The  second 
group  consisted  of  people  who  drank  the  milk  from  tuberculous  cows 
after  heating.  Among  these  there  were  13  cases  of  suspected  tuber- 
culosis. I  have  never  been  able  to  place  much  confidence  in  clinical 
examinations  of  this  sort  and  do  not  consider  that  this  investigation 
has  much  value.  In  the  first  place  it  is  entirely  probable  that  many 
cases  of  infection  escaped  clinical  observation.  We  know  that  many 
people  are  infected  with  tuberculosis  and  recover  without  showing 
clinical  symptoms.  In  the  second  place,  it  is  impossible  from  clinical 
observation  to  tell  the  difference  between  human  and  bovine  tuberculosis. 
The  British  Royal  Commission  has  shown  that  it  is  impossible  to  tell 
the  difference  between  the  two  even  by  microscopical  examination  of 
the  tissues  involved — that  the  process  is  essentially  the  same  whatever 
the  origin  of  the  infecting  organism.  "We  have  had  a  most  striking 
object  lesson  in  the  United  States  showing  the  danger  of  depending 
on  clinical  observation.  In  the  City  of  New  York  the  leading  pedia- 
tricians for  many  years  followed  Koch,  claiming  that  there  was  no 
danger  to  children  from  drinking  the  milk  of  tuberculous  cows.  The 
work  of  Doctors  Park  and  Krumweide  have  shown  how  fallacious  this 
idea  was. 

Taking  the  City  of  New  York  in  general,  these  authors  examined 
88  cases,  of  which  77  were  human  and  11  bovine,  showing  121^  per 
cent  of  bovine  infection.  At  the  Babies'  Hospital,  where  63  cases  were 
examined,  59  were  human  and  4  bovine,  a  percentage  of  6  1-3  bovine. 
At  the  Foundling  Hospital  9  cases  were  examined,  of  which  4  were 
human  and  5  bovine,  or  55  per  cent  bovine.  In  the  Foundling  Hospital 
cow's  milk  was  used  exclusively,  and  these  figures  in  my  opinion  repre- 
sent the  real  danger  from  unprotected  cow's  milk.  These  examinations 
were  made  on  children  who  had  died  of  the  disease.  It  is  well  known 
that  tuberculosis  often  causes  affections  of  bones,  joints,  and  glands, 


M,    P.    EAVENEL,    M.D.  41 

which  are  not  fatal  but  which  lead  to  more  or  less  permanent  deformity 
and  injury.  If  these  cases  are  taken  into  consideration,  the  percentage 
of  bovine  tuberculosis  is  very  much  higher,  probably  about  30  per  cent 
of  those  suffering  from  the  disease. 

A  study  of  age  periods  is  also  very  instructive.  Of  nine  adults 
examined  by  Dr.  Park,  all  showed  the  human  infection.  Of  27  children 
from  5  to  16  years  of  age,  19  showed  human  infection  and  8  bovine. 
Of  18  children  from  birth  to  5  years  of  age,  only  6  showed  human  and 
12  showed  bovine  infection.  Just  why  this  increased  susceptibility 
to  bovine  infection  is  seen  in  children,  and  especially  children  of  the 
younger  age,  I  am  unable  to  explain.  It  is  interesting,  however,  to 
observe  that  it  corresponds  with  the  age  at  which  cow's  milk  forms  a 
considerable  portion  of  the  diet. 

AU  workers  along  these  lines  have  found  figures  corresponding  to 
these,  and  we  are  able  to  say  that  children,  during  the  first  five  years 
of  life,  are  more  suspectible  than  when  older,  and  after  the  age  of  16 
our  figures  show  even  a  smaller  proportion  of  bovine  infection.  The 
figures  collected  by  Dr.  Park  from  laboratories  in  many  countries  show 
the  relation  of  bovine  to  human  infection: 

Cases  Examined     Human  Bovine 

Adults    787                 777  10 

Children,  5-16  years 153                 117  36 

Children,  0-5  years 280          '      215  65 

During  the  last  few  years  very  interesting  work  has  come  to  us 
from  Edinburgh.  The  first  report  is  published  by  Mr.  Fraser.  This 
work  has  an  interesting  and  pathetic  history.  Mr.  Stiles,  the  well- 
known  surgeon  of  Edinburgh,  was  caUed  to  see  a  child  suffering  from 
surgical  tuberculosis.  The  case  was  too  far  gone  for  interference,  and 
soon  went  to  death.  Mr.  Stiles  gave  as  his  opinion  that  the  child  had 
been  infected  by  milk.  This  was  considered  impossible  by  the  parents, 
as  they  had  their  own  cows,  which  were  said  to  have  been  tested  with 
tuberculin.  Mr.  Stiles  persisted  in  his  opinion,  telling  the  parents  that 
if  the  cows  had  not  reacted  it  was  probably  because  the  disease  was  too 
far  advanced.  On  slaughter,  both  cows  were  found  to  be  in  a  condition 
of  advanced  tuberculosis,  and  one  had  tuberculosis  of  the  udder.  The 
bereaved  father  then  gave  money  and  asked  that  a  study  be  made  of 
this  question.  Mr.  Fraser  examined  67  children  12  years  of  age  and 
under,  suffering  from  various  forms  of  surgical  tuberculosis.  Forty-one 
of  these  showed  the  bovine  tubercle  bacillus,  23  the  human  bacillus, 
and  3  both  human  and  bovine.  Analyzing  these  cases  by  age  periods, 
we  find  that  in  children  under  five  years  of  age  there  were  47  cases, 
32  of  which  showed  bovine  infection,  12  human,  and  3  both  human  and 
bovine. 

More  recently  Dr.  MitcheU  of  Edinburgh  has  carried  out  an  investi- 
gation on  cervical  gland  tuberculosis.  Seventy-two  consecutive  cases 
were  examined  by  him.  Sixty-five,  or  90  per  cent,  showed  bovine  infec- 
tion, and  only  7,  or  10  per  cent,  showed  human  infection.    Among  these 


42  SOURCES   OF   INFECTION   IN   TUBERCULOSIS 

there  were  38  cases  in  children  under  5  years  of  age,  and  of  these  35 
showed  bovine  infection  and  only  3  human. 

In  America  Dr.  Lewis  has  examined  15  cases  of  cervical  gland 
tuberculosis,  his  patients  ranging  as  high  as  32  years  of  age.  Among 
these  9  showed  bovine  infection  and  6  human.  Those  showing  bovine 
infection  had  an  average  age  of  8i/^  years,  while  those  showing  human 
infection  averaged  17-2/3  years.  Again  we  note  this  striking  fact  that 
the  younger  the  child  is,  the  greater  apparently  is  the  danger  from 
bovine  infection. 

I  know  of  but  one  piece  of  work  which  does  not  accord  with  these 
general  facts — that  of  Gaffky  of  Berlin.  He  examined  78  children, 
the  ages  not  given  exactly, .  and  among  these  found  only  3  cases  of 
bovine  infection.  These  figures  do  not  agree  with  those  given  by  the 
German  Imperial  Commission  or  by  other  reports  from  Germany.  The 
German  Imperial  Board  of  Health  examined  3  cases  of  primary  cervical 
tuberculosis  and  found  that  two  of  them  were  bovine  and  one  human. 
"Weber  examined  five  cases  II/2  to  8  years  of  age  and  all  of  them  showed 
bovine  infection. 

I  will  not  weary  you  with  further  figures,  and  simply  repeat  the 
statement  that  bovine  infection  seems  much  more  common  in  younger 
children  than  in  older  ones,  and  more  common  in  older  children  than 
in  adults. 

I  know  of  no  explanation  for  the  apparent  immunity  of  adults  to 
infection  by  the  bovine  germ.  We  have  abundant  evidence  that  when 
this  germ  is  inoculated  into  wounds,  as  not  infrequently  happens  to 
veterinarians  and  butchers,  it  produces  exactly  the  same  changes  as  the 
human  germ.  It  is  well  known  that  such  inoculations,  whether  human 
or  bovine,  usually  remain  local  and  do  not  produce  generalized  tubercu- 
losis; yet  we  have  instances  of  such  infections,  with  the  bovine  germ 
extending  up  the  arm  and  producing  generalized  tuberculosis  with  death. 
I  know  of  no  good  reason  why  infection  through  the  digestive  tract 
should  not  also  take  place  in  adults  as  well  as  in  children,  yet  the  fact 
remains  that  laboratory  work  does  not  often  demonstrate  the  presence 
of  the  bovine  germ  in  adults. 

The  question  then  arises,  can  prolonged  residence  in  the  human 
body  change  the  morphology  and  characteristics  of  the  bovine  germ  so 
as  to  make  its  origin  unrecognizable?  I  do  not  hesitate  to  express  my 
belief  that  this  can  and  does  take  place.  I  acknowledge  freely  that  of 
all  germs  the  tubercle  bacillus  seems  to  retain  its  characteristics  as  well 
as  its  virulence  more  strongly  than  any  other.  Yet  we  have  experi- 
mental proof  that  such  a  change  does  take  place.  Dr.  Leonard  Pearson 
and  myself  changed,  by  passage  through  five  calves,  a  typical  human 
germ  into  a  bovine  germ  typical  in  every  respect.  I  know  that  there 
is  a  possibility  of  error  in  this  experiment  but  every  precaution  was 
taken  against  error.  The  calves  were  tested  with  tuberculin,  kept  in  a 
new  stable  with  cement  floor  and  walls,  and  isolated  from  every  known 


M.    P.    RAVENEL,    M.D.  43 

source  of  infection.  Tuberculosis  is  such  a  slow  disease  that  there  is 
always  a  possibility  of  some  error  creeping  in,  in  spite  of  precautions. 

Our  results  have  been  confirmed,  however.  Eber  of  Leipzig  has 
reported  experiments  similar  to  ours,  with  the  same  results.  The  English 
Royal  Commission,  in  studying  the  tubercle  bacillus  isolated  from  cases 
of  lupus  which  did  not  correspond  either  to  the  human  or  to  the  bovine, 
in  two  cases  changed  the  character  of  the  bacillus  by  passage  through 
rabbits  and  calves  until  it  became  a  typical  bovine.  Further  than  this, 
we  know  that  the  avian  tubercle  bacillus  is  derived  from  the  mammalian 
type,  and  that  the  tuberculosis  of  fish  and  of  the  blind  worm  of  MoUer 
have  a  similar  origin  from  the  mammalian  bacillus.  Both  of  these  types 
of  the  tubercle  bacillus  differ  very  much  more  markedly  from  the  mam- 
malian type  than  the  bovine  and  human  differ  from  each  other.  The 
tubercle  bacillus  demands  a  constant  temperature  at  or  about  that  of 
the  body,  yet  by  residence  in  fish  and  in  the  blind  worm  it  can  be  so 
changed  that  it  will  no  longer  grow  at  body  temperature,  but  must  grow 
at  ordinary  room  temperature. 

In  view  of  these  facts,  which  are  acknowledged  by  everyone,  it  does 
not  seem  to  be  going  very  far  out  of  the  way  to  hold  that  the  tubercle 
bacillus  can  be  made  to  change  its  characteristics,  its  morphology  as 
well  as  its  virulence  by  prolonged  residence  in  a  given  soil.  If  it  does 
not  so  change,  it  is  an  exception  to  all  known  germs.  If  such  change 
takes  place,  it  then  follows  that  the  type  of  bacillus  which  is  oftentimes 
isolated  from  the  human  being  and  which  presents  only  the  char- 
acteristics of  the  human  germ  may  in  reality  be  a  bovine  germ  which 
has  changed  its  type  so  that  its  origin  is  no  longer  recognizable  by  our 
usual  methods  of  experimentation. 

The  great  question  now  may  be  asked :  What  proportion  of  the  cases 
of  tuberculosis  occurring  in  human  beings  which  we  see  in  our  actual 
life  and  in  our  practice  are  due  to  bovine  infection?  In  other  words, 
what  is  the  relative  importance  of  infection  from  bovine  sources  to 
infection  from  human  beings?  I  do  not  believe  that  we  have  facts 
enough  before  us  to  make  a  positive  statement  concerning  this  matter. 
We  certainly  must  acknowledge  at  the  present  time  that  infection  from 
our  fellow  man  is  the  most  common  source  of  infection  in  human 
beings,  especially  in  adult  life.  For  children  the  most  sceptical  must 
acknowledge  that  bovine  infection  is  quite  frequent.  In  New  York 
City  the  work  of  Doctors  Park  and  Krumweide  has  demonstrated  that 
at  least  300  children  die  in  that  city  every  year  from  bovine  infection, 
and  Dr.  Park  very  justly  says  that  there  is  no  reason  for  believing  that 
New  York  occupies  any  better  position  in  this  regard  than  other  large 
cities  of  our  country.  The  most  recent  estimate  I  have  seen  is  that 
of  Dr.  Lawrason  Brown  of  Saranac  Lake.  He  considers  it  certain  that 
8  per  cent  of  all  cases  of  tuberculosis  that  we  see  are  of  bovine  origin. 
Accepting  this,  it  means  that  at  least  16,000  people  die  in  the  United 
States   every   year   from  bovine  infection.     This  mortality  is  certainly 


44  SOURCES  OF  INFECTION   IN   TUBERCULOSIS 

great  enough  to  make  us  earnest  in  our  efforts  to  guard  the  people 
against  the  bovine  disease.  Apart  from  the  death  rate,  a  very  much 
larger  number  of  persons  suffer  from  deformities  due  to  tuberculosis, 
such  as  humpback,  hip  joint  disease,  etc.  The  exact  number  of  these 
cannot  be  accurately  estimated. 

If  what  I  have  told  you  is  correct — and  I  feel  that  I  have  given  you 
proofs  of  everything  claimed — the  lesson  to  be  learned  is  a  clear  one. 
We  stand  for  clean  milk — milk  that  comes  from  cows  known  to  he 
healthy — milk  which  is  drawn  and  handled  in  a  cleanly  manner.  We 
must  support  our  health  officers  in  their  work  for  clean  milk,  and  educate 
the  public  in  general  to  support  such  demands.  The  burden  of  the 
proof  must  be  put  on  the  producer.  It  will  not  suffice  to  take  milk  which 
we  do  not  know  to  be  diseased.  We  must  demand  that  milk  be  served 
to  our  communities  which  comes  from  cows  known  to  he  healthy.  The 
value  of  clean  milk,  to  children  particularly,  is  well  known  to  aU.  Its 
influence  in  the  prevention  of  tuberculosis  will  be  equally  great. 


PRESENT  STATUS  OF  IMMUNIZATION  AGAINST 
TUBERCULOSIS 

By  Gerald  Bertram  "Webb,  M.D. 
colorado  springs,  colo. 

The  term  ' '  inmninity, "  as  you  know,  originates  in  the  Latin  ^'im- 
munitas,"  meaning  "free  from  service."  We  apply  it  to  the  condition  of 
an  animal  or  human  being  which  does  not  allow  of  attack  by  bacteria 
or  other  parasites  which  can  cause  disease. 

We  have  a  true  or  natural  immunity  such  as  man  possesses  against 
such  diseases  as  chicken  or  hog  cholera,  or  an  acquired  immunity  such 
as  we  possess  against  smallpox,  after  previous  vaccination  with  cow- 
pox.  Then,  too,  we  have  a  special  tissue  immunity  in  view  of  the  fact 
that  certain  organs  are  more  difficult  to  infect  than  others.  For  instance, 
we  infect  a  guinea  pig  with  tubercle  bacilli.  We  rarely  find  infection  in 
the  kidneys.  In  calves  or  rabbits,  on  the  other  hand,  so  infected,  we 
usually  find  tuberculosis  in  the  kidneys.  In  the  human  being  it  is 
rare  to  find  tuberculosis  of  the  muscles  or  of  the  large  blood  vessels. 

The  history  of  immunity  studies  in  tuberculosis  is  especially  bound 
up  with  American  researches.  To  the  French  must  be  given  credit  for 
the  discovery  that  tuberculosis  is  a  transmissible  disease.  It  was 
proven  by  Villemin  long  before  the  advent  of  the  immortal  Pasteur 
and  long  before  the  discovery  of  the  bacillus  of  tuberculosis  by  the  great 
genius  of  Koch. 

It  is  to  be  recalled  that  the  great  Jenner  lost  a  son  from  tuberculosis 
and  in  his  biography  we  read  that  he,  too,  tried  to  discover  the  cause 
of  tubercles.  Koch  began  the  studies  of  tuberculosis  immunity  by  the 
employment  of  living  cultures,  and  we  can  never  repeat  too  often  the 
laws  he  discovered. 

"  If  a  normal  guinea  pig  is  inoculated  with  tubercle  bacilli,  the  point 
of  inoculation  very  soon  closes.  After  ten  to  fourteen  days  there  appears 
at  this  site  a  small  hard  nodule  which  finally  ulcerates.  This  shows  no 
tendency  to  heal  and  remains  so  until  the  death  of  the  animal.  If, 
however,  an  already  tuberculous  guinea  pig  is  so  inoculated,  while  the 
point  of  inoculation  also  closes,  no  indurated  nodule  appears.  Instead 
a  necrotic  process  of  the  skin  sets  in,  after  the  second  day,  which  finally 
terminates  in  the  casting  off  of  the  slough  and  the  formation  of  a  flat 
ulceration  that  heals  rapidly.  It  does  not  matter  whether  living  or 
dead  tubercle  bacilli  are  used  for  the  second  infection." 

In  this  research,  then,  we  have  a  beginning  of  our  knowledge  of 
immunity  in  tuberculosis,  for  the  first  infection,  although  fatal  in  time, 
evidently  set  in  process  immunity  reactions  which  were  indicated  after 
the  second  inoculation. 

These  studies  led  to  the  development  of  tuberculin  and  to  attempts, 
which  all  failed,  to  prove  immunity  by  the  inoculation  of  dead  products 

45 


46  PRESENT   STATUS  OF  IMMUNIZATION  AGAINST   TUBERCULOSIS 

of  the  germ.  Koch's  final  words  on  immunity  in  tuberculosis  are  worth 
recalling : 

"We  shall  never  obtain  better  results  with  non-living  bacilli;"  and 
"We  shall  not  succeed  in  habituating  the  organism  to  absorbing  entire 
bacilli  which  have  been  injected  subcutaneously  and  by  injecting  small 
quantities  of  them  we  shall  not  habituate  the  organism  to  absorbing 
more." 

Trudeau,  in  1889,  employing  living  bacilli,  immunized  birds  against 
tuberculosis,  and  he  later  stated  that  the  first  encouragement  he  had 
came  only  when  he  began  the  use  of  living  bacilli.  In  1889  also  Dixon 
of  Philadelphia,  working  with  the  branching  forms  of  tubercle 
bacilli,  reported  progress  in  artificial  immunization.  In  1885  Theobald 
Smith  differentiated  the  human  baciUus  from  the  bovine  baciUus  and 
it  was  at  once  natural  to  attempt  to  vaccinate  the  cow  against  tubercu- 
losis by  the  inoculation  of  human  baciUi — so  repaying  that  animal  the 
debt  we  owe  for  smallpox  vaccination. 

Pearson  and  GiUiland  reported  such  work  in  this  country  simul- 
taneously with  von  Behring  and  Koch  in  Germany. 

I  have  recently  received  from  Theobald  Smith  and  from  GiUiland  a 
summary  of  their  respective  work  in  the  immunization  of  cattle  to  tuber- 
culosis by  inoculating  baciUi  of  human  origin. 

Theobald  Smith  reports  that  human  bacilli  could  be  discovered  in  the 
organs  of  cows  some  years  subsequent  to  inoculation,  and  he  states  that 
human  bacilli  cannot  be  employed  to  immunize  cows  against  tubercu- 
losis if  those  animals  are  destined  for  future  dairy  life. 

Calmette  recently  informed  me  at  the  Rome  Congress  that  he  does 
not  believe  that  any  injected  organism  can  destroy  tubercle  bacilli,  and 
for  this  reason  his  attempts  at  the  production  of  immunity  have  been 
via  the  digestive  tract. 

Heymans'  attempts  have  been  most  original.  Heymans  enclosed 
tubercle  bacilli  in  collodion  sacks  and  placed  these  within  the  animal's 
body  so  that  the  blood  juices  might  act  on  the  bacilli  without  infection 
taking  place. 

In  perfecting  the  tubercle  bacillus  as  a  parasite,  nature  has  deter- 
mined that  it  must  have  access  to  and  egress  from  the  organism  attacked, 
and  that  this  germ  must  not  be  too  readily  destroyed  as  it  has  no  life 
history  apart  from  the  diseased  organism. 

Nature  has,  therefore,  caused  the  bacillus  to  build  for  itself  a  pro- 
tective covering  of  wax  which  is  a  highly  resistant  substance.  It  can 
be  estimated  that  at  least  one-third  of  each  bacillus  is  composed  of  wax 
and  fats.  Our  body  cells  have  considerable  difficulty  in  disposing  of 
such  wax,  yet  it  has  been  observed  that  the  lymphocyte  blood  cells  con- 
tain a  ferment — ^lipase — which  can  digest  such  wax. 

Researches  of  Bartel,  Opie,  Bengel,  Marie  and  Fiessinger  all  point 
to  the  lymphocyte  cell  as  the  active  antagonist  in  our  bodies  to  the 
tubercle  baciUus. 


GERALD    BERTRAM    "WEBB,    M.D.  47 

Bartel  showed  that  the  tubercle  bacillus  passing  through  a  mucous 
membrane  becomes  weakened  and  when  it  passes  to  a  lymph  node  it  is 
still  further  weakened.  This  latter  phase  Bartel  speaks  of  as  a  latent 
lymphoid  stage,  and  is  the  stage  which  probably  all  children  develop. 
As  you  know  from  the  researches  of  von  Pirquet  and  others  with  the 
skin  tuberculin  tests,  practically  all  children  by  the  age  of  puberty  are 
infected  with  the  germs  of  tuberculosis. 

Romer,  by  his  recent  work  on  sheep,  indicates  that  such  early  infec- 
tion can  be  in  part  protective  against  further  or  future  disease,  so  that 
we  may  perhaps  interpret  this  early  tubercle  infection  of  childhood  as 
nature's  crude  method  of  vaccination  against  tuberculosis.  That  it  is 
not  a  safe  method,  however,  is  witnessed  by  the  fact  that  large  numbers 
of  children  succumb  to  the  disease. 

Dr.  Sachs  has  spoken  most  kindly  and  in  encouraging  terms  of  our 
attempts  to  study  the  problems  of  immunization  against  tuberculosis, 
and  I  will  briefly  relate  how  we  have  approached  these  studies  and  what 
we  have  accomplished. 

Dwellers  in  high  altitudes  have  for  long  felt  that  they  possessed  a 
higher  immunity  against  tuberculosis  than  dwellers  in  the  lowlands.  As 
you  know,  some  two  thousand  years  ago  Galen  advised  consumptives  to 
sojourn  in  the  high  mountains. 

For  some  decades  certain  blood  changes  have  been  observed  at  high 
altitudes,  such  as  an  increase  in  the  red  blood  corpuscles  and  also  an 
increase  in  the  percentage  of  hemoglobin. 

It  was  our  good  fortune,  however,  to  determine  that  the  lymphocyte 
element  of  the  blood,  above  referred  to  as  being  antagonistic  to  the 
tubercle  bacillus,  was  increased  in  the  circulating  blood  in  the  same 
ratio  as  the  red  corpuscle  was  increased.*  At  an  elevation  of  6,000  feet, 
such  as  Colorado  Springs,  this  increase  amounts  to  some  30  per  cent. 
Another  blood  element,  too  little  studied  but  an  element  which  we 
have  determined  takes  some  part  in  immunity  processes,  the  third  cor- 
puscle of  the  blood  or  blood  platelet,  is  also  increased  in  the  circulating 
blood  at  a  high  altitude. 

Successful  vaccination  of  mankind  against  tuberculosis  is  a  medical 
triumph  long  sought  but  still  long  distant. 

Unfortunately  up  to  now  no  manner  of  inoculating  the  living  tubercle 
bacillus  has  proven  entirely  safe. 

In  general  a  vaccinating  virus  must  be  a  virulent  germ  and  should 
for  a  while  grow  in  the  tissues,  if  possible  at  the  site  of  injection,  thereby 
stimulating  the  production  of  antibodies  by  the  host;  but  this  growth 
of  the  virus  should  be  invariably  destroyed  by  the  injected  animal. 

Some  years  ago  I  watched  Professor  Barber,  with  a  most  original 
technic,  isolate  single  bacteria.  •  It  occurred  to  me  at  once  that  this 
process  might  be  applied  to  the  inoculation  of  animals,  with  first  one 

*  We  have  no-w  another  possible  factor,  observed  by  the  Anglo-American  Physiological 
Expedition  to  Pike's  Peak  three  years  ago,  namely,  the  increased  development  of  the  lung  cells 
which  take  np  the  manufacture  of  oxygen  and  throw  it  into  the  blood  stream. 


48  PRESENT  STATUS  OF  IMMUNIZATION  AGAINST  TUBERCULOSIS 

bacillus,  then  two,  and  by  gradually  increasing  the  number  we  might 
succeed  in  rendering  the  animal  immune. 

Our  first  attempts  were  made  with  anthrax  bacilli  and  mice,  but, 
as  was  shown  later  by  Barber  himself,  with  such  a  very  virulent  organ- 
ism and  with  such  a  small  animal  success  could  not  be  expected.  Inject- 
ing small  numbers  of  human  bacilli  in  a  similar  manner  into  guinea 
pigs  and  monkeys,  we  obtained  a  measure  of  success  in  immunizing 
such  animals.  We  found  that  120  bacilli  injected  at  a  single  dose,  of  the 
culture  employed,  were  necessary  to  produce  disease  in  a  guinea  pig, 
but  that  when  we  began  the  inoculation  with  very  small  numbers, 
cautiously  increasing,  hundreds  of  thousands  of  these  bacilli  could  be 
injected  without  the  production  of  tuberculous  disease. 

A  scientist  who  watched  these  experiments,  himself  dying  of  tubercu- 
losis, requested  that  his  two  children,  aged  nine  months  and  three  years 
respectively,  should  be  submitted  to  a  similar  course  of  inoculation. 
After  four  years  these  two  children  remain  well  and  are  negative  to 
the  skin  tuberculin  test  of  von  Pirquet.  We  were  to  discover,  however, 
in  our  work  that  all  strains  of  tubercle  bacilli  were  not  equally  virulent 
and  it  had  been  our  good  fortune  to  be  employing  a  strain  not  the  most 
virulent. 

We  have  found  various  degrees  in  virulence  of  the  tubercle  bacillus 
by  the  employment  of  the  Barber  technic,  and  from  some  cultures  we 
have  determined  that  ten  bacilli  will  infect  a  guinea  pig  when  inoculated 
at  a  single  initial  dose.  So  far  we  have  failed  to  immunize  guinea  pigs 
by  inoculating  them  with  first  one  bacillus,  then  two,  four,  six  bacilli, 
etc.,  of  such  a  culture.  Lawrason  Brown  has  reported  similar  experi- 
ences. We  have  studied  thirteen  different  cultures  up  to  date  and 
have  found  the  minimum  lethal  dose  to  vary  from  ten  bacilli  to  thirty 
bacilli,  to  fifty  bacilli,  sixty  bacilli,  100  bacilli  and  120  bacilli,  respec- 
tively. 

In  view  of  this  varying  degree  of  virulence  in  cultures  of  the  human 
tubercle  bacillus,  we  have  been  led  to  investigate  whether  the  addition 
of  antagonistic  elements,  such  as  lymphocytes  or  blood  platelets,  might 
allow  us  to  inoculate  safely  a  minimum  lethal  dose  of  the  most  virulent 
tubercle  bacilli. 

Sensitized  vaccines — that  is  to  say  vaccines  made  by  the  addition  to 
virulent  bacteria  of  serum  from  an  immune  animal — have  been  con- 
sidered to  call  forth  better  protective  response  in  some  cases  in  the 
injected  animal  than  the  injection  of  the  bacteria  alone  could  procure. 

Baldwin,  however,  found  that  the  addition  of  serum  from  an 
"immune"  cow  caused  tubercle  bacilli  to  become  even  more  virulent 
to  the  guinea  pigs  he  tested. 

It  is  known  that  tubercle  baciUi  injected  into  the  peritoneal  cavity 
of  a  tuberculous  guinea  pig  become  rapidly  destroyed,  and  it  has  been 
supposed  that  the  mononuclear  or  lymphocyte  type  of  cells  found  here 
was  possibly  responsible  for  this  destruction. 


GERALD   BERTRAM    WEBB,    M.D.  49 

We  inoculated,  therefore,  a  series  of  guinea  pigs  with,  each  100  very- 
virulent  tubercle  bacilli,  with  the  addition  of  a  fluid  rich  in  mononuclear 
cells  derived  from  the  peritoneal  cavity  of  a  tuberculous  guinea  pig. 

We  added  to  this  mixture  in  some  experiments  the  serum  of  an 
immune  pig,  both  heated  and  unheated,  but  again  our  experiments  were 
unsuccessful  and  our  pigs  developed  the  disease  we  were  attempting 
to  protect  them  from. 

In  working  with  the  third  corpuscles  of  the  blood,  or  blood  platelets, 
we  ascertained  the  possible  evidence  that  they  either  carried  or  supplied 
an  immune  body  known  as  opsonin. 

We  then  conducted  a  series  of  experiments  on  guinea  pigs,  inoculat- 
ing them  with  a  small  lethal  dose  of  tubercle  bacilli  (200)  to  which 
were  added  in  some  instances  the  blood  platelets  prepared  from  a  nor- 
mal guinea  pig,  in  other  instances  the  blood  platelets  procured  from  a 
tuberculous  guinea  pig.  Our  results  have,  however,  not  been  con- 
stant, although  we  have  thought  that  the  platelets  possibly  modified  the 
resulting  infection. 

Again  we  have  attempted  in  monkeys  and  guinea  pigs  to  produce 
immunity  by  injecting  a  small  number  (100-200)  of  tubercle  bacilli 
subcutaneously,  and  at  about  the  fourteenth  day  excising  the  result- 
ing local  lesion.  In  every  case  we  have  failed,  as  by  that  time  the 
infecting  organisms  had  reached  the  nearest  lymph  nodes,  or  had  pen- 
etrated even  further. 

Remembering  that  nature  produces  much  fibrosis  in  her  healed 
areas  of  tuberculous  infection,  we  first  produced  scars  by  cuts  or  burns 
on  the  limbs,  and  then  injected  our  minute  infecting  doses  with  some 
difficulty  into  these  scars.  AU  our  attempts  were  fruitless,  all  animals 
becoming  diseased. 

We  are  at  present  attempting  experiments  in  which  we  are  aiming 
at  the  production  of  a  local  lesion  which  can  later  be  excised,  and  at 
the  same  time  we  are  preventing  the  infection  travelling  to  the  regional 
lymph  nodes  and  blood  streams.  The  method  promises  well  and  the 
results  will  be  reported  later. 

Up  to  date,  however,  we  only  offer  the  conclusion  that  by  the  employ- 
ment of  a  culture  which  is  not  too  virulent,  as  tested  by  the  minimum 
lethal  dose,  we  can  procure  by  the  inoculation  of  increasing  numbers  of 
tubercle  bacilli  some  degree  of  immunity  to  tuberculosis. 

We  know  too  that  nature  infects  us  with  very  small  numbers  of 
tubercle  bacilli,  possibly  less  than  ten,  and  it,  therefore,  suggests  itself 
that  by  experimentation  with  such  minute  dosage  of  tubercle  bacilli  we 
may  sometime  achieve  our  goal  of  the  safe  production  of  immunity 
against  tuberculosis.  As  Pasteur  has  so  well  said,  "We  must  repeat 
again  our  experiments.     The  chief  point  to  remember  is  to  persevere." 


ETIOLOGY  AND  MORBID  ANATOMY  OF  BONE  AND 
JOINT  TUBERCULOSIS 

By  Charles  M.  Jacobs,  M.D. 

CHICAGO 

The  manifestations  of  tuberculosis  in  the  human  being  are  the  result 
of  infection  by  either  the  bovine  or  human  tubercle  bacillus.  The 
relationship  of  these  two  types  has  been  the  subject  of  much  investi- 
gation. 

In  1911  the  British  Commission,  after  an  investigation  lasting  ten 
years,  and  at  an  expense  of  seventy-six  thousand  pounds,  reported  that 
three  groups  of  tubercle  bacilli  can  be  isolated  in  the  tuberculous  lesions 
in  man.  Group  One  has  all  the  characteristics  of  the  bovine  type.  Group 
Two  of  the  human  type,  and  Group  Three  has  some  of  the  characteristics 
of  both.  Morphologically  bovine  and  human  tubercle  bacilli  cannot  be 
differentiated,  but  they  are  regarded  as  different  types  of  the  same 
organism.  They  differ  in  their  cultural  characteristics  and  in  their 
power  of  producing  disease  in  different  animals.  The  bovine  tubercle 
bacillus  is  virulent  to  rabbits  in  five  or  six  weeks  after  a  generalized 
tuberculosis  has  occurred,  whereas  the  human  tubercle  bacillus  pro- 
duces a  tuberculous  lesion  in  the  lungs  and  kidneys,  which  rarely  causes 
death. 

The  Commission  further  reported  that  a  very  large  percentage  of 
the  surgical  tuberculosis  was  due  to  bovine  tubercle  bacilli  and  that 
they  rarely  produce  pulmonary  tuberculosis. 

Various  investigators  have  verified  the  findings  of  the  Commission. 
One  investigator  believes  in  a  transitional  type  of  tubercle  bacillus, 
where  transformation  from  the  bovine  to  the  human  tubercle  can  take 
place. 

Fraser,  an  able  assistant  of  Stiles,  studied  the  type  of  tubercle  bacilli 
in  seventy  cases  of  bone  and  joint  tuberculosis  in  children.  The  tuber- 
culous material  obtained  after  operation  was  injected  into  animals,  and 
after  six  weeks  the  animals  were  killed.  The  differentiation  of  the 
organism  was  based  upon  five  tests.  In  forty-one  of  the  cases  the 
bovine  tubercle  was  found;  in  twenty-six  instances  the  human  tubercle 
was  found,  and  in  three  instances  the  mixed  type.  He  investigated  the 
source  of  milk  supply — whether  the  child  had  been  taking  human  or 
cow's  milk.  In  nursing  infants  the  human  tubercle  bacilli  were  found 
in  nineteen  instances  and  the  bovine  bacilli  in  four;  while  in  children 
who  had  been  drinking  cow's  milk,  the  bovine  tubercle  were  found  in 
thirty-seven  instances  and  the  human  tubercle  bacilli  in  seven.  The 
family  history  was  next  investigated  and  he  found  in  twenty-one 
instances  that  there  had  been  pulmonary  tuberculosis  in  the  immediate 
family  in  which  the  child  lived;  the  human  tubercle  bacilli  were  found 
in  fifteen  instances  and  the  bovine  tubercle  bacilli  in  six  instances.     He 

50 


CHAELES    M.    JACOBS,    M.D.  51 

found  that  the  age  was  limited  to  12  years  and  under,  which  he  divided 
into  three  groups.  Group  One  was  of  children  under  3  years  of  age; 
Group  Two  from  3  to  6  years;  Group  Three  from  6  to  12  years.  He 
found  in  Group  One  twenty-three  instances  of  bovine  tubercle  bacillus, 
and  in  five  the  human  tubercle  bacillus.  In  the  second  group  he  found 
the  bovine  tubercle  bacillus  in  nine  and  human  tubercle  bacillus  in  ten ; 
in  the  third  group,  the  bovine  tubercle  bacilli  in  nine  and  the  human 
tubercle  bacilli  in  eleven  instances:  thereby  indicating  that  the  older 
the  child  the  more  often  was  the  human  tubercle  bacillus  found. 

It  may  be  of  interest  to  state  that  in  a  series  of  two  hundred  and 
three  cases  of  bone  and  joint  tuberculosis  treated  by  us  at  the  Home 
for  Crippled  Children,  the  age  was  12  years  and  under.  Statistics  from 
these  will  give  a  good  idea  of  the  age  at  which  bone  and  joint  tuberculosis 
is  most  frequently  seen. 

Age,  Years  Number  of  Cases 

1  to     3  85 

4  to     6  68 

7  to     9  34 

10  to  12  16 

Total  203 

Investigation  showed  that  in  thirty-one  instances  there  was  a  history 
of  pulmonary  tuberculosis  in  sixteen  fathers,  eleven  mothers,  three 
brothers  and  one  grandfather.  In  two  children,  2  years  of  age,  bone 
tuberculosis  developed  within  six  months  after  the  mothers  had  died 
of  pulmonary  tuberculosis. 

There  can  be  no  doubt  that  the  primary  focus  of  infection  in  bone 
and  joint  tuberculosis  is  in  the  lymphatic  glands — particularly  the 
cervical,  mesenteric  and  bronchial.  The  portals  of  entry  of  the  tubercle 
bacilli  are  the  tonsils,  oral  and  nasopharyngeal  cavities,  the  digestive 
and  respiratory  tracts.  As  a  result  of  the  caseation  and  destruction  of 
the  glands  mentioned,  the  bacilli  sometimes  gain  access  to  the  small 
veins  connected  with  them  and  are  probably  carried  to  the  right  side 
of  the  heart,  then  through  the  systemic  circulation  and  distributed  to 
various  parts  of  the  body.  Very  frequently  they  may  be  destroyed  by 
the  proliferating  endothelial  ceUs  as  weU  as  by  the  connective  tissue 
cells  and  leucocytes,  and  if  the  resisting  power  of  the  child  is  enfeebled 
the  bacilli  take  hold  and  a  definite  tuberculous  lesion  is  the  result. 

Various  investigators  have  attempted  to  show  the  type  of  bacilli 
contained  in  these  glands. 

One  investigator  inoculated  guinea  pigs  with  macerated  cervical 
and  mesenteric  glands  from  one  hundred  and  thirty-four  children  who 
had  died.  In  fifty-two  of  the  children  a  tuberculous  process  had  been 
found  at  autopsy — in  twenty-eight  it  was  the  cause  of  death.  Forty- 
six  of  the  guinea  pigs  reacted  to  the  injection  of  both  the  cervical  and 
mesenteric  glands.  The  type  of  organism  was  studied — forty-five  were 
of  the  human  type,  three  the  bovine,  one  the  mixed  type  and  three 
could  not  be  determined. 


52  BONE  AND   JOINT   TUBERCULOSIS 

Mitchell  investigated  seventy-two  unselected  eases  of  tuberculous  cer- 
vical lymph  nodes  in  children.  In  90  per  cent,  of  the  cases  the  bovine 
bacillus  was  found  and  in  10  per  cent,  the  human  bacillus. 

From  these  various  investigations,  what  conclusions  can  be  drawn? 

1.  Bovine  tubercle  bacilli  can  no  longer  be  considered  a  negligible 
factor  in  the  production  of  bone  and  joint  tuberculosis  in  children.  The 
medium  of  infection  is  principally  by  drinking  infected  milk. 

2.  Human  tubercle  bacilli  are  secondary  to  bovine  tubercle  bacilli 
in  the  production  of  bone  and  joint  disease. 

Another  important  question  is:  Just  where  in  the  bones  and  joints 
does  the  disease  begin? 

I  might  start  out  with  the  primary  statement  that  up  to  the  period 
of  ossification  we  never  have  primary  tuberculosis  in  the  epiphysis. 
Why?  Because  the  epiphysis,  being  cartilaginous,  is  never  primarily 
attacked  by  tuberculosis. 

In  adults  the  tuberculous  focus  is  situated  in  the  epiphysis  and 
less  frequently  in  the  synovial  membrane,  whereas  in  children  it  is 
situated  in  the  diaphysis  and  less  frequently  in  the  synovial  membrane. 

While  joint  tuberculosis  may  manifest  itself  as  a  primary  synovial 
disease,  it  is  thought  that  it  is  more  frequently  the  result  of  invasion 
from  an  osseous  focus. 

Stiles  believes  that  the  localization  of  the  disease  is  accounted  for 
by  the  distribution  of  the  three  systems  of  intraosseal  vessels — the 
diaphyseal  or  nutrient,  the  metaphyseal  and  the  epiphyseal  arteries, 
whose  ultimate  branches  anastomose  in  the  region  of  the  metaphyses  of 
bone ;  that  by  whichever  route  the  bacillus  or  embolus  finds  its  way  into 
the  bone,  in  this  last  situation,  it  is  most  likely  to  be  arrested.  The  cir- 
culation being  slow  at  this  point  is  another  circumstance  which  makes 
this  a  favorable  site  for  bacilli.  It  is  a  matter  of  accident,  he  thinks, 
whether  the  disease  begins  in  the  bone  or  in  the  synovial  membrane,  as 
the  blood  supply  is  the  same — the  metaphyseal  and  epiphyseal  arteries 
enter  the  bone  at  the  ligamentous  attachments. 

I  have  felt  very  partial  to  Ely's  theory,  that  the  tubercle  bacilli 
affect  certain  kinds  of  tissue,  those  containing  lymphoid  and  epiphelial 
cells — therefore,  the  bacilli  have  a  predilection  for  red  marrow  and 
synovia;  that  other  tissues — such  as  ligaments,  yellow  marrow,  muscles, 
etc.,  are  immune.  His  theory  seems  plausible  when  we  consider  the 
structure  of  bone.  We  know  that  cancellous  tissue  is  found  in  the 
ribs,  vertebrae,  sterum,  cranial  diploe,  in  the  short  bones,  in  the  shaft 
of  long  bones  in  children  and  in  the  epiphysis  in  adults.  We  also  know 
that  wherever  cancellous  tissue  exists  in  bone  the  marrow  is  red  and 
that  where  yellow  marrow  exists  there  is  no  cancellous  tissue. 

If,  therefore,  Ely's  theory  is  correct,  then  it  seems  to  explain  why 
tuberculosis  occurs  in  the  short  bones,  in  the  diaphysis  of  bone  in  the 
child  and  in  the  epiphysis  in  the  adult. 

At  the  lajst  meeting  of  the  Orthopedic  Section  of  the  American  Medi- 


CHARLES    M.    JACOBS,    M.D.  53 

cal  Association,  Fraser  advanced  the  theory  that  the  pathologic  process 
of  bone  began  in  the  marrow,  but  experimentally  it  was  difficult  to 
infect  the  bone  unless  the  marrow  had  first  been  made  to  undergo  a 
fibro-myxomatous  degeneration;  that  such  a  degeneration  might  result 
from  an  endarteritis  of  nutrient  vessels  or  a  tuberculous  infection  from 
a  neighboring  joint.  He  illustrated  by  lantern  slides  that  a  beginning 
tuberculous  infection  is  a  chronic  endarteritis  in  a  nutrient  vessel. 


NON-OPERATIVE  TREATMENT  OF  TUBERCULOSIS  OF 
BONES  AND  JOINTS 
By  John  L.  Porter,  M.D. 

CHICAGO 

A  long  time  before  the  operative  surgeons  had  progressed  far  enough 
to  operate  upon  tuberculosis  of  the  bones  and  joints  with  any  assurance, 
and  I  thirtk  long  before  the  early  etiology  and  pathology  were  well  under- 
stood, two  facts  which  have  had  great  influence  upon  the  treatment  of 
the  disease  had  been  well  recognized.  The  first  was  that  tuberculosis, 
or  so-caUed  scrofula  of  the  bone  and  joints,  was  a  self-limited  disease. 
The  second  was  that  it  always  resulted  in  deformity. 

Recognizing  those  two  facts,  the  early  orthopedic  surgeons  formu- 
lated a  method  of  treatment  of  tuberculous  bones  and  joints  which 
aimed  to  assist  Nature  to  overcome  the  disease  and  to  prevent,  as  far  as 
possible,  the  development  of  the  deformity.  That  method  of  treat- 
ment was,  among  other  things,  an  important  factor  in  establishing  ortho- 
pedic surgery,  in  its  pioneer  days,  upon  a  solid  foundation  and  we  are 
recognizing  more  than  ever  today  that  the  treatment  of  tuberculosis 
of  bones  and  joints  is  becoming  more  mechanical  and  less  operative,  in  so 
far  as  the  cure  of  tuberculous  infection  and  the  treatment  of  the  deform- 
ity is  concerned. 

Of  course,  conditions  do  arise  in  the  clinical  progress  of  tuberculous 
joints  which  demand  operative  interference,  and  the  most  beneficial 
mechanical  treatment  may  have  to  be  preceded  by  operative  measures 
before  it  can  be  carried  out.  But  the  end  and  aim  of  all  treatment  of 
a  tuberculous  joint,  without  complication,  is  to  put  the  joint  into  the 
best  possible  position  for  future  use,  immobilize  it,  relieve  it  from  fric- 
tion and  assist  Nature  in  every  way  toward  a  spontaneous  recovery. 
The  method  of  immobilizing  a  tuberculous  joint,  preventing  it  from 
functioning  and  preventing  the  development  of  deformity,  will 
depend  upon  the  location  and  extent  of  the  disease  and  the  personal 
preference  of  the  surgeon.  It  makes  little  difference  what  the  individual 
method  is,  so  long  as  it  is  thorough,  efficient  and  continued  for  a  sufficient 
length  of  time.  "While  a  tuberculosis  of  the  spine  may  be  extensive 
enough  to,  demand  prolonged  recumbency  in  bed,  it  is  evident  that 
disease  of  the  knee  or  shoulder  might  be  treated  equally  well  by  some 
mechanical  measures  which  would  permit  the  patient  to  be  up  and  about. 
Although  such  treatment  may,  and  often  does,  require  from  two  to 
five  years,  or  even  longer,  the  time  element,  in  a  child,  is  of  little  import- 
ance when  a  good  functional  result  is  considered — and  a  very  large 
percentage  of  these  cases  do  secure  just  that  result. 

While  early  operation  and  complete  removal  of  a  tuberculous  focus 
in  or  about  a  joint,  is,  theoretically,  a  much  to  be  desired  performance, 
we  have  learned  by   long   and   bitter    experience  that  practically  it  is 

54 


JOHN   L.    POKTER,    M.D.  55 

impossible  in  a  very  large  percentage  of  these  cases.     For  we  are  not 
endowed  with  microscopic  eyes  and  it  is  exceedingly  difficult  to  remove 
all  of  a  tuberculous  focus.     Such  an  operation  almost  invariably  leaves 
the  patient  with  a  stiff  joint  and  frequently  with  discharging  sinuses 
which  have  to  be  dressed  for  years.     Moreover,  such  operations,  espe- 
cially in  the  young  child,  interfere  with  the  growth  and  development 
of  the  bones  involved  and,  at  the  end  of  five  years,  when  the  ultimate 
result  of  the  operation  is  fully  evident,  he  is  no  better  off  and  frequently 
worse  than  he  would  have  been  had  he  spent  that  five  years  in  allowing 
the  joint  to  recover  spontaneously  under  efficient  mechanical  treatment. 
Tuberculosis,  in  some  joints,  has  a  tendency  to  recover  much  more 
promptly  than  in  others.     For  instance,  I  have  frequently  seen  tuber- 
culosis of  the  cervical  spine  and  tarsus  in  children  make  a  complete 
recovery  in  a  year,  with  efficient  immobilization.     As  I  said  before,  the 
method  of  immobilization  is  of  little  importance,  so  long  as  it  is  effi- 
cient and  continuous.     Many  years  ago  surgeons  relied  upon  braces 
and  splints  of  metal  and  leather.     Many  of  these  were  devised  to  per- 
mit of  the  use  of  traction,  with  the  idea  of  separating  the  joint  sur- 
faces and  preventing  friction  and  muscular  spasm.     Some  forty  years 
ago,  the  use  of  plaster  of  Paris  was  made  popular  by  Dr.  Lewis  A. 
Sayre,  of  New  York,  and  since  then  it  has  been  extensively  used  and  is 
today  the  chief  reliance  of  many  orthopedic  surgeons,  especially  during 
the  painful  and  progressive  stage  of  the  disease.    Its  great  advantage  is 
that  it  is  efficient,  comfortable  and  cannot  be  tampered  with  by  the 
patient  or  family,  and,  if  renewed  sufficiently  often  to  carefully  observe 
the  joint  and  care  for  the  skin,  it  is  very  satisfactory  for  the  first  six 
months.     Later,  it  should  be  supplanted  by  braces  or  splints  which  can 
be  removed  at  short  intervals  and  permit  greater  freedom  to  the  muscles. 
When   I   was   in   Liverpool   I  was    much   surprised  to  see  Mr.  Robert 
Jones,  the  busiest  and  most  capable  orthopedic  surgeon  in  Great  Britain, 
treating  hundreds  of  tuberculous  joints  without  a  pound  of  plaster  of 
Paris,  but  he  is  especially  skillful  in  devising  and  applying  mechanical 
splints  for  tuberculous  joints  of  all  kinds,    and  he  apparently  secures 
as  good  results  as  anyone.    Before  plaster  of  Paris  or  any  other  immob- 
ilizing apparatus    is    applied  to  a  tuberculous  joint,  the  muscle  spasm 
which  is  so  characteristic  of  the  disease  is  frequently  so  troublesome  and 
the  resulting  pain  so  distressing  that  it  is  necessary  to  put  the  patient 
to  bed  and  apply  traction  with  a  weight  and  pulley  or  some  mechan- 
ical device,  until  the  spasm  and  pain  are  relieved  and  the  deformity, 
if  any,  is  corrected,  before  applying  mechanical  apparatus.    I  have  said 
little  about  tuberculosis  of  the  joints  in  adults,  but  it  is  undoubtedly  a 
fact  that  they  require  a  longer  time  to  recover  and  operative  interference 
is  indicated  more  frequently  and  earlier  in  the  disease  than  in  children, 
because  the  time  element  to  a  wage  earner  is  of  paramount  importance, 
and  if  he  can  be  enabled  to  get  about,  even  with  a  perfectly  stiff  joint 
or  a  short  leg,  or  even  with  an  artificial  foot,  more  quickly  by  operation 


56  TUBERCULOSIS  OF  BONES  AND  JOINTS 

than  by  mechanical  treatment,  the  operation  should  be  done.  But  in 
children  we  see  tuberculous  joints  recover  from  extensive  disease  with 
a  surprising  degree  of  motion,  and  even  a  little  is  oftentimes  of  great 
advantage.  I  have  been  particularly  impressed  with  the  great  advan- 
tage of  treating  these  cases  in  institutions  which  are  properly  equipped 
not  only  for  the  most  efficient  surgical  and  mechanical  procedures  but 
also  for  the  most  modern,  hygienic-diatetic  treatment.  The  most  ideal 
place  for  these  cases  is  where  they  can  be  given  careful  nursing  and 
medical  supervision  by  attendants  who  are  properly  trained;  where 
those  that  are  confined  to  bed  can  be  taken  out-of-doors;  where  the 
ambulatory  patients  can  be  permitted  to  rest  and  play  in  the  fresh 
air,  and  where  all  can  be  given  fresh  milk,  fresh  eggs,  fresh  vegetables 
and  fresh  air  in  unlimited  quantities.  To  that  end,  I  hope  that  every 
tuberculosis  sanitarium  will  eventually  broaden  its  scope  and  be  pro- 
vided with  the  necessary  equipment  to  admit  cases  of  tuberculous  bones 
and  joints,  as  well  as  tuberculosis  of  other  organs.  "We  have  hospitals 
for  the  special  treatment  of  the  crippled  and  deformed,  and  most  of  our 
general  hospitals  have  wards  for  the  treatment  of  such  patients,  but 
unfortunately  they  are  practically  all  located  in  the  city — most  of 
them  in  the  busiest  parts  of  the  city,  where  land  is  expensive  and  the 
out-of-door's  freedom  which  is  so  beneficial  to  these  patients  is  prac- 
tically nil  or  very  limited.  I  can  conceive  of  no  one  step  which  would 
be  of  so  much  benefit  to  the  large  number  of  poor  patients  afflicted 
with  tuberculous  bones  and  joints  as  the  establishment  of  facilities  for 
their  proper  treatment  in  country  sanatoria. 


SURGICAL  TREATMENT  OF  TUBERCULOSIS  OF 

BONES  AND  JOINTS 

By  Edwin  W.  Rterson,  M.D. 

CHICAGO 

This  is  not  a  competitive  debate,  and  neither  Dr.  Porter  nor  myself 
must  be  understood  as  advocating  either  operative  or  non-operative 
treatment  exclusively. 

It  is  unquestionably  true,  and  it  must  be  distinctly  recognized,  that 
most  cases  of  joint  tuberculosis  in  children  will  get  well  by  mechanical 
non-operative  treatment,  and  the  more  cases  we  can  cure  by  non- 
operative  treatment  the  better.  It  is,  however,  becoming  increasingly 
evident  that  in  adult  joint  tuberculosis,  non-operative  treatment  is  not 
apt  to  be  successful.  It  is  becoming  increasingly  evident  that  the  non- 
operative  treatment  of  joint  tuberculosis,  even  in  children,  requires 
a  very  great  deal  of  time  and  a  very  great  deal  of  care,  and  for  these 
two  reasons  it  is  in  many  cases  impossible  for  a  child  to  get  the  proper 
treatment.  In  some  cases  it  simply  cannot  be  done.  There  are  very 
many  cases  where  from  two  to  six  years  of  surgical  orthopedic  treat- 
ment cannot  be  properly  carried  out  in  an  individual  case.  Is  there 
anything  that  we  can  do  to  help  out  a  child,  who,  for  instance,  has  a 
tuberculous  spine  and  who  cannot  afford  to  pay  $35  or  $40  necessary 
for  a  brace  and  the  necessary  money  each  year  to  have  the  brace  kept 
in  repair  and  to  do  it  for  years,  as  the  child  grows? 

I  believe  that  there  is, — the  operations  for  making  an  artificial  anky- 
losis of  the  spine,  which  have  been  now  for  three  years  under  very  care- 
ful observation.  We  have  done  a  large  number  of  these  operations  in 
this  city,  and  while  it  is  too  early  to  make  any  absolutely  definite  or 
positive  statements  about  the  results,  it  is  safe  to  say  that  many  cases 
have  been  apparently  cured  by  them.  In  brief,  it  is  a  method  of  taking 
a  piece  of  bone  from  the  tibia  with  a  saw  and  sewing  it  into  a  groove 
made  by  splitting  the  spinous  processes  of  the  vertebrae.  This  makes 
for  us  a  splint  and  brace  which  apparently  is  better  than  any  mechanical 
appliance  which  most  of  us  can  apply.  Apparently  children  get  well 
quicker  with  a  splint  of  bone  placed  in  the  spine  than  they  do  with  a 
brace.  I  say  apparently,  because  although  personally  we  only  have 
in  my  clinics  thirty-eight  cases  to  report  upon,  yet  many  of  them  have 
apparently  been  cured  in  six  months,  and  are  today  running  about  with- 
out any  brace.  Most  of  them  seem  perfectly  well  and  have  been  made 
so  with  a  minimum  of  danger  and  with  a  very  slight  operative  risk. 
If  such  results  can  be  made  the  rule,  if  we  can  count  on  getting  such 
results  in  even  a  small  majority  of  cases  with  only  the  small  amount 
of  risk  that  accompanies  even  minor  operations,  I  think  that  if  I  had 
a  child  of  my  own  with  a  tuberculous  spine,  I  should  have  the  operation 
done,  rather  than  the  wearing  of  the  ordinary  external  brace  for 
four  or  five  years. 

57 


58  TUBERCULOSIS  OF  BONES  AND   JOINTS 

I  want  to  speak  of  the  treatment  of  the  tuberculous  joints  in  adults 
because  to  my  mind  it  is  radically  different  from  the  treatment  in 
children.  In  tuberculous  joint  disease,  we  do  not  get  cures  by  mechan- 
ical treatment  alone  in  the  enormous  majority  of  cases.  Personally, 
I  have  been  doing  orthopedic  work  for  sixteen  or  more  years,  and  I  have 
not  seen  an  adult  with  a  tuberculous  hip  or  a  tuberculous  knee  get 
well  without  operation.  I  believe  I  have  seen  a  tuberculous  spine  get 
well,  but  time  enough  has  not  really  elapsed  to  show  whether  these  adult 
cases  are  well  or  not. 

The  very  pertinent  question  comes  up :  "  When  is  an  adult  not  an 
adult ;  when  is  a  child  not  a  child  ? ' '  And  that  is  what  we  cannot  pos- 
sibly state,  except  arbitrarily.  In  looking  over  my  series  of  cases  I 
have  failed  to  find  any  child  over  16  years  who  has  gotten  well  from  hip 
or  joint  tuberculosis,  really  well,  I  mean,  without  operation.  The  right 
way  to  treat  an  adult  tuberculous  joint  is  to  make  that  joint  stiff  and 
solid,  just  as  soon  as  possible,  because  an  adult  joint  will  not  get  well 
from  joint  tuberculosis  with  a  useful  range  of  motion  in  the  vast 
majority  of  cases.  The  best  way  to  hold  an  adult  tuberculous  joint 
still  is  to  make  a  bony  ankylosis  in  a  favorable  position.  It  can  be  done 
very  readily  in  the  hip,  by  the  method  of  Albee,  of  New  York,  who  has 
devised  an  excellent  operation  which  I  have  successfully  done  in  several 
cases.  In  the  knee  joint  it  is  extremely  easy  and  safe  to  make  an  anky- 
losis and  in  an  adult  tuberculous  knee  the  quicker  you  make  an  anky- 
losis the  better,  just  as  in  the  hip.  You  do  not  need  to  try  to  curette 
it  out  or  scrape  it  out,  because  no  surgeon  can  remove  all  the  tuber- 
culous material  that  is  in  the  joint. 

In  the  case  of  ankle-joint  tuberculosis,  I  am  obliged  to  take  a  very 
radical  position,  because  I  have  had  a  large  number  of  ankle  joint  tuber- 
culosis cases  to  treat  in  adults.  Nearly  all  of  these  have  had  abscesses 
and  sinuses,  and  all  of  them  belonged  to  the  working  classes,  where  time 
and  money  were  lacking.  Most  of  them  came  to  me  after  years  of  con- 
servative treatment,  with  the  disease  steadily  growing  worse,  and  I 
advised  and  performed  amputation,  with  the  most  satisfactory  results. 
The  other  operative  methods  which  may  be  necessary  in  complications, 
such  as  paralysis,  etc.,  I  will  not  enter  into  at  all.  I  will  simply  say 
that  there  is  no  one  treatment  for  all  kinds  or  all  individuals  afflicted 
with  joint  tuberculosis.  "We  simply  have  to  do  the  best  thing  we  can 
for  the  patient,  according  to  our  judgment.  If  you  cannot  cure  the 
disease  in  any  other  way,  amputate  as  soon  as  you  can.  Many  adult 
cases  are  treated  conservatively  for  too  long  a  time.  You  cannot  ampu- 
tate a  spine,  of  course,  but  you  can  amputate  legs. 

DISCUSSION 

Dr.  John  Ridlon,  Chicag'O :  I  am  fully  in  accord  with  what  has  been 
said  by  Dr.  Jacobs  and  Dr.  Porter,  but  I  must  oppose  much  that  has 
been  said  by  Dr.  Ryerson. 


DISCUSSION  59 

It  should  be  remembered  that  patients  suffering  from  tuberculous 
joints  are  also  suffering  from  the  disease — tuberculosis — and  that  any 
cure  or  apparent  cure  of  the  local  manifestation  in  the  joint  is,  as  a  rule, 
only  temporary,  unless  the  patient  has  also  been  cured  of  his  disease — 
tuberculosis. 

Many  years  ago  Wright,  of  Manchester,  England,  thought  he  could 
cure  early  joint  tuberculosis  by  extensive  excisions  of  the  diseased 
joints,  but  it  was  found  that  the  disease  returned  in  the  majority  of 
cases,  no  matter  how  thorough  the  operation  may  have  been. 

Then  Battle,  of  London,  demonstrated  that  excised  tuberculous 
joints  required  a  longer  period  of  immobilization,  after  the  excision, 
to  complete  the  cure  than  did  joints  that  had  not  been  excised. 

At  the  present  time,  the  advanced  operators,  like  Dr.  Ryerson,  do 
not  attempt  to  remove  all  the  diseased  bone  when  operating  to  immob- 
ilize these  joints.  Indeed  some  think  that  the  less  bone  removed,  the 
better.  Doubtless  this  is  so;  and  that  we  may  hope  that  the  time  will 
soon  come,  as  it  has  already  come  in  operations  on  tuberculous  spines, 
when  no  bone  is  removed  at  all. 

In  speaking  of  Albee's  operations  to  immobilize  tuberculous  spines 
and  joints.  Dr.  Ryerson,  quite  unintentionally  I  think,  used  a  very 
felicitous  expression.  He  spoke  of  "Dr.  Albee's  fictitious  mind."  I 
would  hardly  go  as  far  as  that,  but  would  say  "fictitious  theories."  I 
am  sure  Dr.  Ryerson 's  impatience  to  gain  quick  results  is  responsible  for 
his  never  having  seen  tuberculosis  of  the  ankle  recover  without  opera- 
tion. I  have  seen  tuberculosis  of  the  ankle  with  five  sinuses  recover  with- 
out deformity  and  with  good  motion,  having  had  no  treatment  of  any 
kind  whatever.  I  believe  that  operations  should  be  done  on  tuberculous 
joints  only  as  a  life-saving  measure.  Never  in  thirty-six  years  of  active 
work  have  I  seen  a  tuberculous  ankle  that  required  operation;  and 
never  but  one  knee  and  one  hip.  As  to  tuberculosis  in  adult  patients, 
my  experience  again  differs  from  the  opinion  expressed  by  Dr.  Ryerson. 
I  am  sure  that  adult  joint  tuberculosis  recovers  quite  as  promptly  and 
quite  as  perfectly,  under  non-operative  treatment,  as  does  the  disease 
in  children.  He  admits  having  seen  some  perfect  results  in  spinal 
tuberculosis.  I  have  exhibited  such  cases  at  meetings  where  he  has 
been  present,  and  I  shall  have  great  pleasure  in  showing  him  similar 
results  in  hip,  knees  and  ankles.  It  seems  to  me  to  be  a  great  mistake 
at  a  meeting  of  this  kind,  where  many  laymen  are  present,  to  let  the 
impression  go  uncontradicted  that  the  only  way  to  treat  tuberculosis  of 
the  joints  is  to  destroy  them  by  a  bloody  and  dangerous  operation. 


NON-TUBERCULOUS  LESIONS  OCCURRING  IN 

TUBERCULOSIS 

By  Joseph  Zeisler,  M.D. 

CHICAGO 

I  cannot  very  well  see  why  a  patient  suffering  from  generalized 
tuberculosis  should  not  be  affected  by  any  of  the  well-known  skin  dis- 
eases. You  are  all  aware  of  the  fact  that  a  patient  who  has  pulmonary 
tuberculosis  is  inclined  to  excessive  perspiration  and  conditions  result- 
ing from  this  are  frequently  found  in  such  patients.  I  have  in  mind 
one  condition  which  might  be  pointed  out  and  which  is  known  by  the 
name  of  Pityriasis  Versicolor,  an  affection  of  the  skin  appearing  in 
patches  on  the  chest  or  back;  light  brown  or  sometimes  a  little  darker 
patches  which  can  be  easily  scraped  off  and  show,  under  the  microscope, 
vegetable  fungi.  But  even  in  the  case  of  Tinea  Versicolor,  you  will  find 
it  often  enough  in  people  who  present  not  even  a  suspicion  of  tuber- 
culosis, but  who  perspire  freely. 

The  subject  of  tuberculosis  of  the  skin  is  one  of  comparatively 
recent  date.  Looking  back  a  little  over  thirty  years  we  find  that  only 
one  form  of  tuberculosis  was  recognized,  but  since  that  time  the  sub- 
ject has  assumed  enormous  proportions,  and  from  year  to  year  its 
importance  has  increased.  This  is  due  very  much  to  the  fact  that 
finer  methods  of  diagnosis  have  been  introduced.  When  we  depended 
chiefly  upon  the  verification  of  tubercle  bacilli  in  pathologic  lesions, 
when  we  recognized  forms  of  tuberculosis  only  in  dermatoses  in 
which  this  organism  could  be  easily  and  assuredly  detected,  the  list  was 
not  very  large;  but  since  the  finer  methods  of  Pirquet,  Calmette  and 
Moro  and  particularly  the  injection  of  tuberculin  as  a  method  of  reac- 
tion have  been  introduced,  it  has  been  found  that  many  diseases  of  the 
skin  were  intimately  related  to  tuberculosis  in  which  this  previously 
had  not  even  been  suspected. 

I  do  not  know  whether  my  esteemed  colleague,  who  is  to  follow  me, 
will  consider  that  I  am  trespassing  upon  his  ground  when  I  under- 
take to  say  a  few  words  about  certain  affections  in  tuberculosis  which 
are  not  classed  as  tuberculosis  proper  but  as  so-called  tuberculides; 
but  I  am  sure  his  phase  of  the  subject  is  sufficiently  large. 

By  tuberculides  we  mean  cutaneous  affections  in  which  Koch's 
bacillus  is  not  found,  as  a  rule,  but  which  react  positively  against  one 
or  another  of  the  tests  which  I  have  just  mentioned. 

To  cite  one  illustrious  example,  a  subject  in  regard  to  which  a  con- 
siderable change  of  opinion  has  taken  place,  particularly  within  the  last 
few  years,  I  would  mention  Lupus  Erythematosus.  Lupus  Vulgaris,  as 
has  been  known  for  many  years,  is  a  true  form  of  tuberculosis,  a 
standpoint  which  was  not  held  generally,  even  in  1884,  when  Kaposi 
denied  stoutly  that  Lupus  Vulgaris  had  any  connection  with  tuber- 

60 


JOSEPH   ZEISLER,    M.D.  61 

culosis.  As  regards  Lupus  Erythematosus,  a  fight  has  been  waging,  on 
and  off,  for  many  years ;  but  today  some  of  the  most  conservative  der- 
matologists are  strongly  inclined  to  class  it  as  one  of  the  tuberculides, 
because  many  of  the  cases  react  against  the  injection  of  tuberculin 
positively. 

Another  example  is  a  disease  of  the  skin,  known  as  Lichen  Scrofu- 
losorum,  first  described  by  Hebra,  who  meant  to  convey  the  idea  that 
it  was  found  in  scrofulous  subjects  but  was  not  itself  a  form  of 
tuberculosis.  For  years  and  years  the  position  of  this  disease  was 
uncertain,  as  tubercle  bacilli  were  rarely  found  in  the  lesions,  but  in 
more  recent  years  the  reaction  of  patients  affected  by  this  disease  against 
tuberculin  injections  has  been  so  frequently  positive  that  today  Lichen 
Scrofulosorum  is  classed  with  the  tuberculides. 

I  would  also  remind  you  of  Acne  Varioliformis,  called  by  this  name 
because  its  lesions  resemble  those  of  variola  or  smallpox.  It  is  a  some- 
what unusual  disease,  occurring  in  the  form  of  pustules  tending  to  necro- 
sis upon  the  forehead,  the  scalp,  the  nose  and  occasionally  upon  the 
back;  a  disease  which  has  also  been  called  acne  necrotica  by  Boeck,  of 
Christiania.  This  dermatosis  has  been  gradually  taken  over  into  the 
field  of  tuberculosis. 

Another  disease,  of  somewhat  obscure  nature,  and  rather  rare,  has 
been  described  as  "Erytheme  indure  des  scrophideux"  by  Bazin.  Its 
nature  has  been  misunderstood  for  many  years.  Not  so  very  long  ago, 
in  1896,  at  the  London  International  Congress,  when  instances  of  this 
disease  were  demonstrated,  a  famous  dermatologist  would  pass  by  and, 
with  a  sweep  of  the  hand,  say  "mercurial  plaster,"  indicating  that  he 
considered  them  gummatous  syphilides.  This  Erythema  Induratum 
is  today  classed  with  tuberculosis. 

Another  disease,  which  was  known  for  many  years  and  was  described 
first  by  Hebra  under  the  name  of  Acne  Cachecticorum,  is  practically  a 
generalized  form  of  acne  consisting  of  papulonecrotic  lesions,  in  subjects 
who  are  run  down,  and  is  today  well  recognized  as  one  of  the  tuber- 
culides. These  patients  react  distinctly  and  positively  against  tuber- 
culin injection. 

Some  other  more  unusual  diseases  which  Barthelemy  described  under 
the  name  of  FoUiclis  and  Acnitis,  show  lesions  in  the  first  instance 
upon  the  surface  in  general;  in  the  second,  especially  in  the  face.  The 
nature  of  these  diseases  has  not  been  thoroughly  understood  until 
recent  years,  when  their  relation  to  tuberculosis  has  been  established. 

There  is  no  doubt  that  Eczema  often  occurs  in  tuberculous  patients. 
We  know,  in  fact,  a  distinct  form  of  Eczema  in  infants,  which  we  consider 
as  scrofulous  eczema,  and  I  have  usually  been  able  to  identify  it,  not 
only  by  an  enlargement  of  the  glands  but  also  by  its  peculiar  location, 
around  the  nostrils,  corners  of  the  mouth,  ears,  etc.  This  distribu- 
tion alone  should  arouse  your  suspicions  as  to  the  cause  being  scrofu- 
losis,  which,  as  you  know,  is  a  form  of  tuberculosis  in  children,  patho- 


62  TUBERCULOUS  LESIONS 

logically  identical  with  tuberculosis,  yet  which  I  still  believe  it  is  wise, 
from  a  clinical  point  of  view,  to  separate  from  tuberculosis  in  general, 
on  account  of  its  benign  character. 

That  other  diseases  of  the  skin  may  and  do  occur  in  tuberculous  sub- 
jects, we  have  no  special  reason  to  doubt. 


TUBERCULOUS  LESIONS 
By  Oliver  S.  Ormsby,  M.D. 

CHICAGO 

The  subject  of  tuberculosis  of  the  skin  is  a  large  one.  It  is,  there- 
fore, difficult  even  to  outline  it  in  a  few  minutes. 

There  are  two  classes  of  disorders  that  must  be  discussed  in  this 
connection:  the  one  in  which  the  bacillus  of  tuberculosis  is  present 
in  individual  lesions;  the  other,  which  is  produced  by  the  toxins  of 
the  bacillus  when  the  latter  is  in  a  distant  focus.  I  shall  limit  what 
I  have  to  say  to  a  brief  description  of  the  disorders  commonly  acknowl- 
edged to  be  tuberculous  and  induced  by  the  local  action  of  the  tubercle 
bacillus. 

Although  we  are  all  more  or  less  familiar  with  the  symptoms  of 
these  various  disorders,  I  think  it  is  proper  to  make  a  resume  of  them. 

The  first  and  most  important  of  the  tuberculous  disorders  of  the 
skin  is  lupus  vulgaris.  For  many  years  it  was  described  as  an  entity, 
and  not  connected  with  tuberculosis,  but  for  some  time  now  it  has 
been  acccepted  by  all  as  being  of  tuberculous  origin.  The  disease 
usually  occurs  in  children,  at  least  it  commonly  begins  in  childhood, 
and  attacks  the  face,  about  the  nose  more  often  than  other  parts.  Occa- 
sionally the  disorder  begins  in  adult  life,  and  very  often  extends  to 
adult  life  from  childhood.  Other  areas  that  may  be  involved  are  the 
neck,  ears,  extremities,  and  various  parts  of  the  trunk.  Many  names 
have  been  given  to  the  various  manifestations  of  this  disease.  A  patch 
of  lupus  presents  the  following  features :  It  begins  as  a  small,  brown- 
ish-red, slightly  elevated  spot  in  the  skin,  which  soon  becomes  covered 
with  a  scale.  This  gradually  spreads  peripherally  until  an  area  the  size 
of  a  dime  or  silver  quarter,  or  larger,  becomes  involved.  Under  pres- 
sure with  a  glass  (diascope),  apple- jelly-brown  nodules  may  be  seen 
throughout  the  patch.  These  are  soft  in  consistency  and  are  character- 
istic of  the  disease.  The  disease  spreads  very  slowly,  and  requires  a 
number  of  years  to  produce  even  a  moderate-sized  patch,  as  a  rule.  In 
certain  cases,  the  infiltration  spreads  as  an  even  brown  discoloration,  in 
place  of  the  small  nodules  before  mentioned.     At  times,  on  the  neck  or 


OLIVER   S.    ORMSBT,    M.D.  63 

trunk  or  other  situations,  the  disease  spreads  peripherially  and  heals 
in  the  center,  producing  a  serpiginous  configuration  in  which  syphilis  is 
closely  simulated.  In  certain  cases  of  lupus  a  marked  connective-tissue 
new-growth  occurs,  producing  the  hypertrophic  variety;  in  others, 
changes  occur  which  induce  marked  deformity;  in  still  others,  by  ab- 
sorption of  tissue  about  the  end  of  the  nose,  a  deformity  is  produced 
suggesting  the  parrot's  beak.  The  lupus  patch  may  become  the  seat  of 
other  changes,  producing  varieties  known  as  lupus  verrucosus,  and  lupus 
papillomatosus.  Other  descriptive  terms,  such  as  lupus  nodosus,  oedema- 
tosus,  tumidus,  elephantiasicus,  etc.,  are  applied  to  those  cases  assuming 
these  forms. 

In  this  country,  ulceration  is  not  as  frequent  as  it  is  abroad,  and 
while  the  name,  lupus,  suggests  an  ulcer,  we  more  often  see  the  non- 
ulcerated  types  before  mentioned.  The  common  conception,  therefore, 
that  lupus  means  an  open  ulcer  often  leads  to  the  error  of  classing  in 
this  category  the  superficial  epitheliomata  or  skin  cancers  that  occur 
in  people  around  and  past  40  years  of  age.  The  brownish-red,  scaly 
patch  of  lupus,  with  the  soft  nodules  shown  under  the  diascope,  is  very 
different  from  the  hard  nodules  or  ulcerated  area  surrounded  by  a 
pearly  margin  which  is  found  in  epithelioma;  and  is  also  quite  different 
from  the  circinate,  indurated  nodules  of  syphilis,  which  only  remain  in 
one  area  a  short  time,  undergo  ulceration,  and  heal,  developing  in  a  new 
situation,  or  rather,  situations.  At  times  a  deeply-situated,  ulcerated 
lupus  of  the  nose  may  be  strongly  simulated  by  a  gummatous  syphilide 
of  the  same  area.  The  rapidity  of  the  destructive  process  in  the  latter, 
as  well  as  the  probable  bone  involvement,  makes  the  differentiation 
between  the  two. 

In  a  second  variety,  there  occur  warty  lesions,  classified  as  tubercu- 
losis verrucosa  cutis.  This  variety  always  follows  inoculation.  There 
are  two  forms  described — one,  the  anatomical  tubercle  or  post-mortem 
wart,  which  usually  occurs  on  the  hands  of  people  handling  dead  bodies. 
The  lesions  in  this  variety  are,  therefore,  about  the  backs  of  the  fingers 
and  dorsal  surface  of  the  hands.  The  lesion  begins  as  a  small  papulo- 
pustule, which  spreads  peripherally  and  soon  becomes  verrucous  or 
warty.  It  is  only  moderately  elevated  and  usually  comparatively  dry 
and  very  slightly  inflammatory.  Marked  exceptions,  however,  to  this 
rule  occur.  In  some  cases  a  reddish  halo  surrounds  the  lesion,  but  the 
miliary  abscesses  so  common  to  blastomycosis  are  rarely  seen  here.  These 
lesions  usually  develop  to  the  size  of  a  dime  or  a  little  larger,  and  then 
remain  stationary. 

A  second  more  extensive  variety,  described  by  Riehl  and  Paltauf, 
occurs  not  only  on  the  backs  of  the  hands  but  also  on  other  parts  of  the 
body,  including  the  forearm,  thighs  and  trunk.  The  patches  in  these 
cases  are  larger  than  those  just  described,  are  more  papillomatous,  and 
are  apt  to  have  a  greater  amount  of  purulent  discharge.  They  present, 
however,  the  same  verrucous  appearance,  and  are  microscopically  iden- 
tical. 


64  TUBERCULOUS  LESIONS 

Verrucous  tuberculosis  is  found  frequently  in  certain  mining  dis- 
tricts where  pulmonary  tuberculosis  is  common,  and  is  said  to  be  induced 
by  the  miners  wiping  their  mouths  with  the  backs  of  their  hands 
after  having  expectorated  discharges  loaded  with  the  bacilli.  Cases 
are  on  record  of  this  variety  being  produced  by  the  bovine  tubercle 
bacillus,  such  a  group  having  been  recorded  by  Lassar.  The  progress 
of  these  cases  is  slow  and  the  subjective  symptoms  are  practically  nil. 
As  the  disease  spreads  peripherally,  healing  occurs  in  the  center,  result- 
ing in  a  certain  amount  of  scar  formation. 

A  third  variety  is  that  termed  scrofuloderma.  In  this  variety, 
infection  of  the  skin  with  the  bacillus  of  tuberculosis  always  occurs  by 
direct  contiguity  with  some  structure  beneath  the  skin.  The  com- 
monest sources  for  this  infection  are  the  glands  about  the  neck,  the 
various  joints,  and  some  bones.  There  is  a  variety  which  occurs  first 
as  subcutaneous  tuberculous  gummata  which,  by  extension  upward,  sec- 
ondarily involve  the  skin,  producing  the  same  type  of  lesion  as  the 
others.  The  ulcers  that  occcur  in  the  scrofulodermata  are  irregular  in 
outline,  have  soft,  often  undermined  edges,  their  floors  frequently  per- 
forated by  sinuses  leading  to  structures  beneath,  and  their  secretion  is 
usually  a  thin,  muco-purulent  or,  occasionally,  hemorrhagic  discharge. 
Not  infrequently  bridges  of  tissue  extend  across  the  ulcer,  which  have 
not  been  destroyed.  Occasionally  a  tuberculous  lupus  nodule  may  be 
found  about  the  edge  of  the  ulcer,  showing  the  identity  of  the  etiology 
of  the  two  conditions. 

A  fourth  variety  is  that  form  which  usually  occurs  about  the  muco- 
cutaneous orifices,  and  is  represented  by  ulcers.  It  is  sometimes  called 
orificial  tuberculosis,  or  miliary  tuberculosis  of  the  sMn,  or  simply 
tuberculous  ulcers.  In  these  cases,  the  lesion  begins  as  a  small  nodule 
which  breaks  down  rapidly,  producing  an  ill-kept  ulcer  with  soft,  irreg- 
ular margins  and  unhealthy  floor,  one  which  gradually  spreads  and 
rarely  heals.  These  ulcers  occur  always  in  the  subjects  of  tuberculosis 
— in  the  throat,  the  intestinal  tract,  or  other  internal  organs  having  con- 
nection with  the  surface  by  way  of  mucous  membranes.  As  a  rule  they 
are  small,  but  occasionally  by  peripheral  spreading  and  coalesence  of 
several  lesions  large  surfaces  may  be  covered.  In  addition  to  the  muco- 
cutaneous orifices,  the  lesions  may  occur  about  the  nose  and  face  and 
other  regions. 

In  addition  to  the  classical  varieties  mentioned  above,  it  is  important 
for  us  to  recognize  that  several  other  forms  of  tuberculosis  occur.  There 
is  a  disseminated  lupus  which  occurs  in  patches  presenting  the  usual 
apple-jelly,  brown  lupus  nodule,  pretty  generally  distributed  about  the 
body,  frequently  following  an  attack  of  measles.  Many  such  cases  are 
recorded,  particularly  in  England. 

Certain  cases,  also,  of  erythema  induratum  of  Bazin  are  undoubtedly 
tuberculous;  that  is,  they  are  induced  by  the  bacillus  of  tuberculosis  in 
the  lesion.  Others  of  these  cases  are  unquestionably  tuberculides. 
Finally,  some  of  these  eases  can  be  placed  in  the  group  of  sarcoides. 


WILLIAM    ALLEN   PUSET,    M.D.  ^^^Qo 

There  are  several  other  rare  forms  which  hardly  need  be  described 
today.  In  the  microscopic  study  of  tuberculosis  of  the  skin,  it  is  found 
that  the  baciUi  occur  in  very  small  numbers  in  lupus.  They  are  some- 
what more  abundant  in  the  verrucous  varieties  and  also  in  scrofulo- 
derma, and  are  quite  abundant  in  the  orrficial  variety.  On  the  other 
hand,  giant-cell  formation  is  common  in  lupus,  while  the  so-called  cheesy 
degeneration  common  to  internal  tuberculosis  is  found  only  in  the  mil- 
iary or  orificial  variety  in  the  skin.  The  best  method  for  finding  the 
bacilli  is  by  the  use  of  antiformin.  In  this  way  the  tissue  is  dissolved 
and  the  bacilli  are  left  in  the  solution. 

Recent  findings  which  deserve  further  investigation  and  which  may 
solve  some  of  the  problems  relative  to  the  apparent  scarcity  of  the 
baciUi  in  these  lesions  concern  the  granules  described  by  Much.  These 
granules,  which  are  of  different  forms,  have  been  found  by  this  observer, 
as  weU  as  by  several  others,  in  aU  tuberculous  conditions,  and  occur 
either  in  association  with  or  independently  of  the  acid-fast  baciUi.  They 
are  gram-positive,  and  have  been  found  in  some  of  the  conditions  hereto- 
fore described  as  tuberculides.  For  example,  in  lupus  %nilgaris  a  very 
few  acid-fast  bacilli  may  be  found,  with  a  much  greater  number  of  the 
gram-positive  granules  of  Much.  By  the  antiformin  method  this  has 
been  done  several  times,  and  in  certain  diseases,  such  as  lupus  erythema- 
tosus, in  which  the  bacillus  of  tuberculosis  is  not  found,  these  granules 
have  been  found.  The  question  is  still  open,  but  it  is  worth  the  atten- 
tion of  those  interested  in  tuberculosis,  as  these  granules  may  be  a  form 
of  the  tubercle  bacillus. 

Neither  the  true  tuberculosis  of  the  skin  nor  the  tuberculides  are  as 
common  here  as  they  are  abroad,  although  during  the  course  of  a  year 
a  number  are  seen.  However,  we  are  all  struck  by  the  difference  in  the 
number  of  cases  shown  here  and  those  shown  in  various  parts  of  Europe. 
Men  like  Dr.  Zeisler,  whose  early  training  was  had  in  Europe,  cannot 
help  but  note  this  difference.  Notwithstanding  this  fact  there  are  a 
sufficient  number  to  warrant  our  attention  and  to  demand,  at  least  to  a 
certain  degree,  a  knowledge  of  their  symptoms. 


TREATMENT  OF  CUTANEOUS  TUBERCULOSIS 

By  William  Allen  Pusey,  M.D. 

CHICAGO  ' 

From  the  standpoint  of  treatment,  there  are,  speaking  generally, 
two  forms  of  tuberculosis  of  the  skin:  (1)  True  tuberculosis  of  the 
skin,  usually  occurring  in  the  form  of  lupus  \nilgaris;  and  (2)  scrofulo- 
derma, in  which  the  skin  is  involved  secondarily  as  the  result  of  an 


66  TREATMENT    OF    CUTANEOUS   TUBERCULOSIS 

underlyiiig  focus  of  tuberculosis,  usually  a  tuberculous  gland  or  bony 
structure.  This  latter  condition  hardly  belongs  to  us.  Its  treatment 
is  usually  surgical  and  is  a  question  of  the  treatment  of  the  primary 
deeper  lesion  of  tuberculosis.  I  shall,  therefore,  leave  scrofuloderma 
out  of  consideration  and  confine  myself  to  the  treatment  of  lupus. 

The  treatment  of  lupus  has  been  one  of  the  unsatisfactory  things 
in  medicine.  The  reason  is  this:  The  lesions  show  an  almost  malignant 
tendency  to  spread  and  to  recur.  One  tubercle  develops  after  another, 
slowly  and  painlessly,  but  persistently,  and  do  what  we  may  in  the 
way  of  chemical  or  mechanical  destruction,  the  disease  goes  on  with  the 
formation  of  tubercles  in  new  areas,  or  the  development  of  tubercles  in 
the  scars  of  previous  lesions,  and  so  cases  used  to  go  on  year  after  year, 
gradually  producing  deformity  that,  in  the  worst  cases,  was  hideous. 
But  to  return  to  our  point,  we  never  knew  when  we  were  done  with 
a  case,  because  the  disease  was  always  recurring,  after  destructive 
measures  and  so  the  treatment  was  unending. 

We  entered  into  a  new  era  in  the  treatment  of  tuberculosis  of  the 
skin  when  Finsen  discovered  that  the  lesions  could  be  destroyed  by 
exposure,  under  certain  conditions,  to  intense  degrees  of  ultra  violet 
light.  The  older  methods  had  consisted  of  all  sorts  of  mechanical  and 
chemical  destructive  measures.  This,  of  course,  carried  the  disfigure- 
ment of  the  patients  often  further  than  the  original  disfigurement  by 
the  disease. 

In  addition  to  relative  permanency  of  results,  the  Finsen  method 
of  treatment  with  ultra  violet  light  does  not  destroy  the  healthy  tissue 
in  which  the  tubercles  are  imbedded,  so  it  does  not  add  to  the  disfigure- 
ment; but,  on  the  contrary,  produces  a  relative  improvement  in  the 
contour  of  the  involved  parts. 

There  have  been  some  improvements  in  technique  in  Finsen 's  method 
and  considerable  improvement  in  apparatus,  but  no  improvement  in  the 
principles  involved;  and  Finsen 's  method  of  treatment  of  lupus  is  vir- 
tually the  last  word  on  the  subject. 

Radium  and  X-rays  can  be  used  in  the  same  way.  There  are  no 
essential  differences  in  the  results,  except  insofar  as  they  are  on  the 
side  of  Finsen 's  method  with  ultra  violet  light. 

The  introduction  of  the  principle  of  treating  lupus  by  exposure  to 
radiant  energy  of  high  actinic  properties  was  the  introduction  of  a 
new  principle  in  the  treatment  of  skin  diseases ;  and  Finsen,  who  intro- 
duced this  principle,  was  a  real  benefactor  of  the  human  race.  In  this 
country,  where  we  have  little  squalor,  lupus  is  uncommon  and  Finsen 's 
benefaction  is  not  of  such  obvious  importance,  but  in  the  densely  popu- 
lated districts  of  Europe,  with  their  poverty-stricken  people,  Finsen 's 
discovery  has  given  an  amount  of  relief  to  a  horrible  disease  that  makes 
the  discovery  stand  out  as  one  of  the  very  important  contributions  to- 
therapeutics  in  the  nineteenth  century. 


TREATMENT  OF  CUTANEOUS  TUBERCULOSIS  67 

DISCUSSION 

Dr.  Theodore  B.  Sachs:  I  would  like  to  ask  Dr.  Zeisler  to  define, 
ia  a  brief  way,  the  five  or  six  conditions  that  he  mentioned. 

Dr.  Zeisler :  I  simply  desired,  in  my  remarks,  to  present  the  general 
scope  of  these  affections,  but  would  be  very  glad  to  supplement,  in  a 
very  few  words,  these  various  forms. 

I  have  never  had  any  difficulty  in  pronouncing  the  word  cachectic, 
as  some  seem  to  have.  As  far  as  describing  Acne  Cachecticorum,  it  is 
really  a  peculiar  disease  of  the  skin,  more  or  less  generalized  over  the 
extremities  and  somewhat  over  the  trunk,  and  consists  of  lesions  which, 
in  themselves,  are  very  much  like  those  in  ordinary  acne — namely, 
small  pustules  which  in  this  case  are  somewhat  flabby  and  show  little 
tendency  to  heal,  but  tend  to  break  down  and  so  form  scars.  This 
is  usually  found  in  patients  who  are  very  badly  run  down. 

The  condition  which  I  mentioned  as  Acne  Varioliformis  is  really 
one  of  the  most  characteristic  diseases  of  the  skin.  It  can  easily  be  rec- 
ognized by  its  peculiar  location.  It  generally  occurs  upon  the  fore- 
head, upon  the  skull,  occasionally  upon  the  nose  and  occasionally  upon 
the  back.  The  lesions  run  a  course  very  much  like  that  of  variola  or 
smallpox,  except  that  a  scab  forms  which  sometimes  remains  for  weeks 
or  even  months  before  it  finally  drops  off  and  leaves  a  scar.  This  is 
not  common  here ;  I  have  seen,  in  my  thirty  years  of  practice  here,  about 
a  dozen  cases  of  it. 

Lupus  Erythematosus  which  I  also  mentioned,  is  a  well-known  form, 
probably  known  to  all  medical  people  here, — a  disease  which  often  has 
the  appearance  of  a  butterfly — that  is,  starting  over  the  bridge  of  the 
nose  and  spreading  over  the  cheeks  in  the  form  of  two  wings.  Isolated 
patches  occur  upon  the  scalp  and  behind  the  ears,  but  very  rarely  upon 
the  body. 

Another  form,  which  I  mentioned,  namely  Folliclis,  consists  of 
small  papules,  necrotic  lesions,  usually  on  the  extremities,  which  have 
a  tendency  to  break  down  and  naturally  leave  scars. 

Question  :  Do  you  find  any  particular  racial  exhibition  of  these  dis- 
eases, or,  in  other  words,  do  these  diseases  occur  in  the  colored  race? 

Dr.  Ormsby:  I  have  no  statistics  relative  to  the  proportion  of  cases 
which  occur  in  the  races,  but  that  aU  varieties  of  tuberculosis,  as  well 
as  the  tuberculides,  do  occur  in  the  colored  race  there  is  no  doubt.  In 
fact,  some  of  the  most  remarkable  cases  that  have  been  used  for  illus- 
tration of  these  diseases  have  occurred  in  that  race.  Concerning  the  sus- 
ceptibility of  the  skin,  I  do  not  believe  the  problem  has  been  worked 
out. 

Dr.  Zeisler:  The  tendency  in  modern  times  has  been  very  strong 
to  generalize  the  treatment  of  all  forms  of  tuberculosis.  Of  course, 
when  we  have  an  individual  localized  patch  of  lupus  or  other  forms 


68  TREATMENT  OF   CUTANEOUS  TUBERCULOSIS 

of  tuberculosis,  intensified  local  treatment  seems  to  suggest  itself 
promptly;  viz.,  excision,  chemical  destruction  and  phototherapy. 

The  treatment  by  tuberculin  is  being  frequently  employed,  and  I 
have  in  mind  one  interesting  case,  which  I  managed  about  a  year  ago. 
It  was  a  very  remarkable  case, — a  young  gentleman  from  Indiana,  who 
for  ten  years  had  had  all  sorts  of  lesions,  tending  to  appear  on  his  body, 
particularly  in  the  axillary,  inguinal  and  gluteal  regions.  Opera- 
tion after  operation  was  performed  upon  him ;  all  kind  of  vaccines  were 
used,  but  a  clear  diagnosis  was  not  made.  When  this  case  came  under 
my  observation,  I  immediately  diagnosed  it  as  Lichen  Scrophulosorum. 
He  was  sent  to  the  Michael  Reese  hospital.  All  kinds  of  tests  were  made 
in  order  to  verify  my  diagnosis,  but  at  first  without  result.  After  two 
days  I  received  a  telephone  message  from  my  son,  who  was  an  interne 
there  at  the  time,  saying,  "Father,  I  congratulate  you.  We  found 
tubercle  bacilli  in  the  discharge  from  the  cutaneous  abscesses."  From 
then  on  I  started  to  treat  this  patient  by  injections  of  tuberculin, 
beginning  with  a  small  amount  and  carrying  it  up  to  the  point  of  tol- 
erance. Some  surgical  work  was  done  by  Dr.  Willys  Andrews,  and  the 
injections,  combined  with  other  measures,  brought  about  a  cure  in  this 
case  in  the  course  of  six  months. 

Treatment  of  this  sort  must  be  done  in  a  careful  manner,  and  I 
believe  some  preparations  have  become  so  reliable  that  today  we  may 
consider  tuberculin  as  an  important  factor  in  the  management  of  many 
forms  of  tuberculosis. 


THE  LAEYNX  IN  THE  EAELY  STAGES  OF  PULMONAEY 

TUBERCULOSIS 

By  Elmer  L.  Kenyon,  M.D. 

CHICAGO 

It  is  safe  to  say  that  a  meeting  like  this,  devoted  exclusively  to 
the  discussion  of  tuberculosis  of  the  larynx,  would  never  have  been  held, 
if  it  were  not  for  pulmonary  tuberculosis.  For  the  question  of  tuber- 
culous laryngitis,  exclusive  of  pulmonary  tuberculosis,  is  so  rare  as  to 
be  an  academic  rather  than  a  practical  question.  "While  primary 
laryngeal  tuberculosis  is  not  at  all  impossible,  and,  according  to  observ- 
ers, has  been  demonstrated,  yet  the  conditions  under  which  it  would 
be  likely  to  be  produced  are  so  difficult  of  fulfillment,  except  through 
the  conditions  present  in  pulmonary  tuberculosis,  that  it  must  occur 
as  a  primary  disease  only  with  extreme  rarity.  Laryngeal  tuberculosis 
should  be  looked  upon  from  both  a  scientific  and  a  practical  standpoint 
almost  exclusively  as  a  complication  of  pulmonary  tuberculosis. 

One  who  watches  the  larynges  of  case  after  case  of  pulmonary  tuber- 
culosis in  the  earlier  stages  becomes  convinced  of  the  great  relative 
resistance  of  the  larynx  to  tuberculous  infection.  One  sees  the  larynx 
literally  bathed  in  tuberculous  infection  day  after  day  for  weeks  and 
months,  without  succumbing  to  the  invader.  But,  on  the  other  hand, 
while  its  resistance  to  tuberculous  infection  is  much  greater  than  is  the 
resistance  of  pulmonary  tissue,  yet  its  resistance  is  remarkably  less  than 
that  of  the  other  structures  in  the  upper  air  passages.  The  only  pos- 
sible exception  to  this  statement  is  the  tonsil;  but  our  knowledge  of 
tuberculosis  of  the  tonsil  in  early  pulmonary  tuberculosis  is  too  slight 
for  careful  comparison.  The  study  of  the  possible  explanation  for  the 
yielding  of  this  naturally  resistant  mucous  membrane  to  tuberculous 
invasion,  while  a  similar  mucous  membrane  in  the  adjacent  structures 
holds  out  against  infection,  is  one  of  my  purposes  in  this  discussion. 

We  may  presume  that  the  larynx  starts  out  in  pulmonary  tubercu- 
losis as  a  normal  structure;  but  the  conditions  are  such  that  after  a 
certain  number  of  weeks  the  larynx  is  practically  never  a  normal  struc- 
ture. The  continual  wear  and  tear  caused  by  the  forcing  of  the  abnor- 
mal secretion  of  the  lungs  through  the  larynx  results,  in  practically 
every  ease  of  pulmonary  tuberculosis,  after  some  weeks,  in  a  larynx 
which  is  not  normal. 

What  are  the  abnormal  conditions  which  we  find  in  the  larynx  after 
a  certain  number  of  weeks  of  pulmonary  tuberculosis?  Hyperaemia  of 
a  dusky  character  is  extremely  common,  affecting  all  parts,  but  most 
often  the  arytenoid  region.  Transient  but  persistent  acute  hyperaemia 
is  common.  In  winter,  such  an  acute  hyperaemia  is  practically  universal 
in  patients  who  live  out-of-doors  in  this  climate ;  it  is  probably  protective 
in  its  effects.    Roughening  of  the  cords,  with  at  times  actual  paresis,  and 

69 


70  THE  LARYNX,  EST  PULMONARY  TUBERCULOSIS 

with  resulting  tendency  to  aphonia,  is  seen  and  is  capable  of  complete 
recovery  without  local  infection  with  tuberculosis.  And,  more  than  all 
of  these,  we  find  infiltration  in  the  posterior  upper  parts  of  the  larynx. 
This  is  variable  in  degree  and  affects  particularly  the  inter  arytenoid 
and  the  arytenoid  region  itself;  the  infiltration  of  the  aryteno-epiglot- 
tic  fold  is  comparatively  rare.  These  infiltrations  evidently  follow  a 
great  deal  of  wear  and  tear  in  the  larynx  and  occur  in  different  pul- 
monary, or  laryngeal,  affections;  in  pulmonary  tuberculosis  they  prob- 
ably never  are  wholly  absent  after  a  certain  duration  of  the  pulmonic 
disease. 

Considering  now  the  engrafting  of  tuberculous  infection  in  the 
larynx  through  local  mucous  membrane  infection,  what  is  the  mechan- 
ism of  the  process  ?  Through  the  wear  and  tear  resulting  in  the  abnor- 
malities mentioned,  one  must  suppose  that  the  resistance  of  the  epi- 
thelium to  infection  becomes  impaired.  The  superficial  cells  are  injured 
and  possibly  form  a  less  thick  layer  of  resistant  tissue.  In  proportion 
as  this  injury  becomes  an  actual  abrasion  is  tuberculous  infection  to  be 
feared.  Indeed,  it  is  safe  to  say  that  in  the  earlier  stages  of  pul- 
monary tuberculosis,  tuberculous  infection  from  the  lumen  of  the 
larynx  does  not  occur,  except  through  an  actually  injured  mucous 
membrane.  The  irregularity  of  the  laryngeal  surface,  by  harboring 
secretion,  undoubtedly  encourages  infection.  But  the  fact  is  true,  like- 
wise, of  the  mouth  and  nose,  which  are  not  so  readily  infected  with  tuber- 
culosis. Motion  as  a  factor  in  disturbing  the  already  abnormal  mucous 
membrane  is  worthy  of  careful  consideration.  The  motion  of  talking 
affects  not  only  the  larynx  but  also  the  soft  palate  and  the  tongue; 
and,  moreover,  the  movement  in  the  larynx  from  talking  is  not  violent, 
and  the  edges  of  the  vocal  cords  are  not  brought  into  contact  roughly. 
While  talking,  in  connection  with  the  irregularity  of  the  larynx  and 
the  abnormality  of  the  mucous  membrane,  may  well  be  looked  upon 
as  a  factor  in  the  injury  of  the  mucous  membrane,  which  results  in  tuber- 
culous infection,  yet  there  occurs  another  form  of  motion  in  the  larynx 
which  probably  is  more  important.  I  refer  to  cough.  What  occurs  in 
the  larynx  when  one  coughs?  With  the  quick  inhalation  the  larynx 
is  forcibly  pulled  downward  by  the  extraneous  down-pulling  group  of 
muscles  and,  as  it  were,  braces  itself  for  what  is  to  follow.  At  once 
the  cords  strike  forcibly  together  and  hold  firmly  against  the  contrac- 
tion of  the  walls  of  the  chest  upon  the  accumulated  air,  forcing  it  against 
the  resistant  cords;  then,  instantly,  the  larynx  violently  opens  and  the 
air  bursts  through.  This  motion  is  not  only  more  violent  than  the  motion 
of  talking,  but  it  is  commonly  repeated  over  and  over  during  each  day. 
The  cords  not  merely  touch  but  they  are  driven  firmly  together  and 
hold  against  a  pressure  from  below;  the  mucous  membrane  of  the  edges 
of  the  cords  are  much  more  likely  to  be  injured  than  they  are  from 
talking.  Moreover,  the  movement  of  the  larynx  in  the  arytenoid  region 
is  much  more  violent  than  in  talking.    Here,  where,  as  Dr.  W.  E.  Cassel- 


ELMEB   L.    KENYON,    M.D.  71 

berry  has  well  pointed  out,  the  infiltration  of  the  mucous  membrane 
has  resulted  in  diminishment  of  flexibility,  cracks  or  other  abrasions 
are  very  likely  to  result  from  violent  and  often  repeated  motion. 

One  thought  more.  What  is  the  function  of  the  laryngologist  in  pul- 
monary tuberculosis?  The  function  of  the  laryngologist  is,  to  use  a  lo- 
cally popular  phrase,  to  be  "the  watch  dog  of  the  larynx."  The  larynx 
should  be  watched  as  faithfully  as  the  obstetrician  watches  the  urine 
of  his  patient  for  albumen.  It  is  the  business  of  the  laryngologist 
to  know  when  the  larynx  is  approaching  a  condition  which  puts 
it  in  imminent  danger  of  tuberculous  invasion.  It  is  his  business 
to  know  at  the  earliest  possible  moment  when  tuberculosis  has  actually 
taken  root  in  the  larynx.  If  it  be  true  that  local  treatment  of  the  larynx, 
after  weeks  of  infection,  results  in  benefit  to  the  larynx  in  tuberculosis, 
then  it  is  more  true  that  local  treatment  of  the  larynx  may  result  in 
healing  the  roughened  or  cracked  mucous  membrane  before  the  tuber- 
culosis has  become  engrafted.  If  it  be  true  that  local  treatment,  after 
weeks  of  laryngeal  tuberculosis,  is  capable  of  improving  the  tubercu- 
losis of  the  larynx,  then  it  is  all  the  more  capable  of  benefitting  this 
form  of  tuberculosis  when,  through  the  close  watching  of  the  larynx, 
one  is  able  to  institute  treatment  at  once,  or  very  soon  after  tuber- 
culosis has  become  engrafted.  One  should  watch  the  larynx  in  pul- 
monary tuberculosis,  know  what  is  going  on,  and  when  suspicious  con- 
ditions arise  take  care  of  them  and  not  wait  until  tuberculosis  is 
established  and  extended.  If  careful  consideration  of  the  general  and 
pulmonary  condition  of  many  patients  is  capable  of  enabling  us  to 
prevent  pulmonary  tuberculosis,  or  if  it  is  desirable  to  diagnose  pul- 
monary tuberculosis  early,  then  it  is  likewise  practicable  and 
desirable  in  pulmonary  tuberculosis,  by  keeping  close  watch  of  the 
larynx  in  individual  cases,  either  to  prevent  the  advent  of  the  infection 
of  the  larynx  with  the  tuberculous  germ,  or  if  engrafted,  to  make  the 
diagnosis  early  and  to  institute  treatment  when  treatment  is  most  likely 
to  succeed. 

I  would,  then,  to  conclude,  emphasize  two  thoughts, — one  concern- 
ing the  probable  especial  bearing  of  cough  on  the  infection  of  the 
larynx  with  tuberculosis  in  pulmonary  tuberculosis;  and,  second,  the 
need  of  routine  watching  of  the  larynx  in  every  case  of  pulmonary 
tuberculosis. 


SYMPTOMS  AND  DIAGNOSIS  OF  LARYNGEAL 

TUBERCULOSIS 

By  E.  Fletcher  Ingals,  M.  D. 

CHICAGO 

For  the  detection  of  the  earliest  manifestations  of  tuberculosis,  it 
is  important  that  the  physician  should  be  an  expert  diagnostician  in  dis- 
eases of  the  nose,  the  throat  and  the  chest ;  otherwise  he  is  liable  to  error 
at  the  very  time  when  his  knowledge  would  be  of  the  greatest  service 
to  the  patient. 

Later  in  the  disease,  the  well  qualified  general  practitioner  will  only 
rarely  find  much  difficulty  in  making  a  correct  diagnosis;  but  even 
then  there  are  some  cases  in  which  the  evidence  is  very  confusing, 
so  that  it  may  be  difficult  to  decide  between  certain  cases  of  simple 
chronic  catarrhal  infiammation,  malignant  disease,  syphilis,  lupus  and 
tuberculosis. 

This  statement  applies  largely  to  diseases  of  the  upper  air  passages 
only,  but  it  is  also  often  true  of  the  manifestations  of  disease  of  the  lungs. 

The  physician  should  begin  his  examination  with  a  careful  analysis 
of  the  history,  including  heredity,  from  the  early  childhood  of  the 
patient,  for  not  infrequently  the  hereditary  tendency  or  the  effects  of 
some  previous  disease  may  prove  one  of  the  vital  factors  in  the  evidence, 
and  occasionally  even  peculiarities  of  absolutely  healthy  individuals 
must  receive  judicious  consideration  before  a  correct  decision  can  be 
formed.  I  cannot  too  strongly  insist  upon  these  statements,  but  I  will 
not  take  your  time  by  going  into  detail.  I  will  confine  myself  to  the 
more  salient  features  of  the  diagnosis. 

Having  critically  considered  the  history  and  subjective  symptoms, 
the  physician  should  address  himself  to  a  careful  examination  of  the 
objective  signs  of  departure  from  health,  never  forgetting  normal  vari- 
ations from  the  typically  perfect  form.  As  an  illustration  of  the  need 
of  this  latter  precaution  in  diagnosis,  I  may  mention  one  of  the  common 
errors  made  by  those  who  specialize  in  diseases  of  the  nose.  In  exam- 
ining the  naris,  they  find  a  more  or  less  prominent  spur  projecting  from 
one  side  of  the  septum  and  many  at  once  decide  that  it  should  be 
removed,  totally  ignoring  the  fact  that  such  obstructions  are  present  in 
50  per  cent,  of  the  Caucasian  race,  and  that  in  nearly  all  of  these  they 
have  not  the  slightest  effect  upon  the  individual's  health  or  happiness, 
if  they  are  let  alone. 

The  early  symptoms  of  tuberculous  laryngitis  are  like  those  of  an  ordi- 
nary cold,  which  continue  for  several  weeks,  usually  attended  by  hacking 
cough  but  with  little  or  no  expectoration.  These  symptoms  may  con- 
tinue for  several  months  before  they  attract  serious  attention.  Early 
there  is  sometimes  a  peculiar  weakness  of  the  voice  and  often  the 
patient  is  hoarse.     There  is  loss  of  strength  and  weight,  hardly  appre- 

72 


E.    FLETCHER   ENGALS,    M.D.  73 

ciable  in  the  beginning,  usually  attended  by  some  rapidity  of  pulse, 
and  often  by  slight  elevation  of  temperature  in  the  afternoon,  from 
one-half  to  one  degree. 

As  the  disease  progresses,  the  symptoms  become  more  and  more  pro- 
nounced and  the  patient  usually  develops  the  symptoms  of  pulmonary 
tuberculosis.  Emaciation  occurs,  the  appetite  is  impaired  and  pro- 
gressive weakness  occurs,  cough  is  more  frequent  and  productive,  and, 
if  ulceration  takes  place,  pain  in  the  larynx  is  generally  experienced 
in  swallowing,  and  tenderness  may  be  present  on  palpation.  In  some 
advanced  cases  with  extensive  ulceration,  the  dysphagia  becomes  most 
distressing,  often  so  great  that  the  patient  will  gradually  starve  rather 
than  eat;  but  the  amount  of  pain  depends  largely  upon  the  location 
of  the  ulcer.  Sometimes  a  large  ulcer  may  cause  but  little  inconven- 
ience, while  a  small  one  located  differently  may  be  very  painful. 

The  pulse,  in  advanced  cases,  usually  runs  from  120  to  140  per 
minute  and  daily  afternoon  fever  of  two  or  three  degrees  is  common; 
the  skin  is  sallow,  hot  and  dry,  or  at  times,  especially  at  night,  bathed 
in  profuse  perspiration. 

In  nearly  all  cases  of  laryngeal  tuberculosis,  superadded  to  the 
laryngeal  symptoms  are  those  of  pulmonary  tuberculosis,  which  gen- 
erally precedes  the  laryngeal  trouble ;  however,  the  latter  may  often  be 
detected  before  the  pulmonary  signs  have  attracted  any  attention. 

In  advanced  cases,  dyspnoea  is  often  present,  generally  due  to 
weakness  and  pulmonary  involvement ;  but  in  a  small  percentage  of  cases 
it  results  from  swelling  with  obstruction  of  the  glottis.  When  swelling 
of  the  upper  part  of  the  larynx  prevents  its  closure  during  deglutition, 
fluids  leak  into  the  trachea  and  cause  distressing  spasms  of  cough.  The 
tenacious  secretion,  during  the  later  stages,  often  causes  a  very  annoy- 
ing and  sometimes  painful  cough  that  is  frequently  productive  of 
vomiting  and  thus  hastens  the  progressive  emaciation  and  adynamia. 

Anaemia  of  the  mucous  membrane  of  the  nasal  cavities,  but  more 
especially  that  of  the  palate,  is  often  one  of  the  earliest  signs  of  the 
disease. 

The  larynx  itself  may  be  either  pale  or  of  a  dull  red  color,  but  the 
congestion  is  very  rarely  of  the  bright  color  that  characterizes  acute 
and  sometimes  chronic  catarrhal  laryngitis,  and  it  also  differs  from  the 
dull  red  color  found  in  most  malignant  affections  of  the  organ. 

One  very  suggestive  sign  that  marks  the  very  beginning  of  a  lim- 
ited number  of  cases  of  tuberculosis  of  the  upper  air  passages  is  a  peculiar 
thinness  or  atrophy  of  the  laryngeal  walls,  which  may  appear  not 
more  than  a  third  to  half  as  thick  as  normal.  This  condition,  when 
present  and  associated  with  the  pallor  already  referred  to,  is  almost 
pathognomonic.  In  some  cases,  a  diffused  dull  congestion,  not  only 
of  the  cords  but  of  the  upper  part  of  the  larynx,  coupled  with  diffused 


74  SYMPTOMS    AND    DIAGNOSIS    OF    LARYNGEAL    TUBEECULOSIS 

or  local  thickening  of  from  25  to  50  per  cent,  is  one  of  the  signs  that 
appear  during  the  first  year.  This  is  attended  by  sluggish  movements 
of  the  cords  which  cause  the  hoarseness. 

Impaired  mobility  of  the  larynx,  due  to  involvement  of  the  muscles, 
associated  with  feeble  voice  and  some  hoarseness,  sometimes  appears  to 
be  one  of  the  first  evidences  of  tuberculous  laryngitis,  but  the  sign  is 
not  characteristic  and  must  not  be  given  weight,  except  as  associated 
with  other  signs. 

During  this  early  stage  elimination  of  gastro-intestinal  and  renal 
disease  and  critical  examination  of  the  lungs,  aided  by  the  tuberculin 
test,  are  most  important  in  reaching  an  accurate  diagnosis.  Later  on 
pale  dense  swelling  of  the  epiglottis  and  the  characteristic  pyriform 
swelling  of  one  or  both  ary-epiglottic  folds ;  and  the  thickened  posterior 
commissure,  bathed  in  grayish  mucus  or  a  more  yellowish  muco-pus, 
are  pathognomonic.  The  swollen  parts  occasionally  appear  much  like 
oedema,  but  in  nearly  all  cases  the  observer  gets  the  impression  of 
solidity  of  the  parts.  Only  one  of  these  parts  may  be  swollen,  but  usually 
two  or  more  are  involved.  With  this  condition  ulceration  is  usually 
present. 

The  ulcers  are  generally  superficial,  1  to  2  mm.  deep,  with 
worm-eaten  edges  and  irregular  yellowish  gray  surfaces.  The  ulceration 
commonly  begins  on  the  venticular  band  and  ere  long  involves  the  oppo- 
site side,  the  posterior  commissure  and  the  true  cords.  It  is  significant 
that  in  tuberculosis  ulceration  ordinarily  begins  at  the  lower  part  of 
the  larynx,  while  in  syphilis  it  is  apt  to  start  on  the  epiglottis. 

In  a  small  percentage,  tuberculous  ulcers  may  be  3  or  4  nun. 
in  depth,  like  specific  ulcers;  but  I  do  not  remember  having  seen 
any  of  them  with  the  sharp  or  undermined  edge  so  common  in  syph- 
ilis. Not  infrequently  there  are  tuberculomas  of  a  cord  or  of  the  poste- 
rior commissure.  These  are  apt  to  have  an  ulcerated  surface.  I  have 
occasionally  seen  an  acute  tuberculous  follicular  inflammation  of  the  epi- 
glottis, characterized  by  dull  congestion  and  swelling,  with  several  yel- 
lowish gray  patches  in  appearance  much  like  those  of  follicular  tonsi- 
litis.  This  is  usually  attended  by  much  pain  and  in  my  experience 
has  commonly  been  followed  by  rapid  superficial  ulceration,  spreading 
from  point  to  point. 

The  symptoms  and  signs  I  have  mentioned  will  be  sufficient  to  estab- 
lish the  diagnosis  in  the  great  majority  of  cases,  but  there  are  very  rare 
cases  in  which  syphilis  and  tuberculosis  are  combined  that  will  demand 
a  most  searching  examination. 

In  other  cases,  of  comparative  frequency,  we  must  distinguish  between 
chronic  catarrhal  laryngitis,  syphilitic  laryngitis,  lupus,  cancer  and 
tuberculous  laryngitis.  The  salient  features  of  these  various  affections 
are  most  effectively  presented  in  tabular  form  as  follows : 


Chronic  Catarrhal 
Laryngitis 

Syphilitic 
Laryngitis 

Cancer  of 
Larynx 

History    

Of    repeated 
colds  

Of   syphilis   if   we   can 
get  the  truth 

Gradually  increasing 
hoarseness. 

Weakness,  ema- 
ciation,  fever. . 

Negative   .... 

Early  negative 

Negative  until  late  in 
disease. 

Hoarseness    . . . 

Usual  but  vari- 
able   

Usual     after     a    few 
weeks 

Commonly  an  early  symp- 
tom. 

Cougli 

Common,  often 
paroxysmal. 

Not  significant 

Not  significant. 

Pain   

Negative   .... 

Often  none,  seldom  se- 
vere   

Negative  early  in  most 
cases:  later  common 

Color  and  form. 

Uniform, 
bright     con- 
gestion;   mod- 
erate   thicken- 
ing    of     cords 
and    possibly 
walls     or 
larynx 

Dull     congestion     and 
thickening,  especially 
of  epiglottis.      Ulceration 
begins    early    usually    at 
upper     part     of     larynx. 
Scars     often     found     in 
fauces    

Localized  usually  lateral 
induration  and  thick- 
ening of  a  dull  red  color. 
Usually  involves  vocal 
cord  and  parts  just  above 
it.    No   cicatrices. 

Ulceration 

Absent 

Common     in      tertiary. 
Ulcers    progress    rap- 
idly  3   or  4  mm.    Deep, 
sharp,         punched-out 
edges.    Tendency  to  heal 
under  proper   treatment. 

Usual  after  five  months; 
destruction;  no  tenden- 
cy to  heal;  possibilities 
of     Aberhalden     reactions. 

Syphilitic 
Laryngitis 

Lupus 
of  Larynx 

Tuberculous 
Laryngitis 

Tests,  etc 

Therapeutic    and 
Wasserman 
tests    

History    

Negative   . . .  . 

Negative 

Gradual    impairment    of 

voice  and  slight  constitu- 
tional  disturbance. 

Weakness,  ema- 
ciation, fever. 

Negative   .... 

Negative  for  years 

Early,  slight;  become 
more  marked  in  a  few 
months. 

Hoarseness 

Usual    

Occasionally   present; 
commonly  absent .... 

May  be  slight  or  absent 
for  a  few  mouths.  Later, 
persistent  and  progressive. 

Pain   

Usually      ab- 
sent   

Negative 

Negative  during  first  few 
months.  Persistent  and 
severe  later  after  ulcera- 
tion. 

Color  and  form. 

Congestion, 
thicken- 
ing     ulcera- 
tion or  scars 
in  advanced 
cases  

Scars    where    healed. 
Thickening;     one     or 
more  nodules  usual  on 
surface    or    edge    of 
ulcer    

Early  sometimes  pale 
atrophied;  usually  lo- 
calized dull  congestion  and 
thickening.  Later  pale 
pyriform    swelling   of    ary- 

epiglottic  folds ;  this  is 
semi-translucent  but  ap- 
pears solid  as  compared 
with  oedema.  Disease  usu- 
ally begins  at  lower  part 
of  larynx. 

Ulceration  .... 

Common    in 
advanced  .  . 

Always    present;    indo- 
lent  nodules    on   sur- 
face or  edges ;    tendency 
to  heal  at  one  part  while 
progressing  elsewhere. 

Superficial  grayish  yel- 
low ulcers  1  or  2  mm. 
deep,  irregular  worm- 
eaten  edges  and  surface. 
Very  little  tendency  to 
heal  unless  marked  consti- 
tutional improvement  oc- 
curs. 

Tests 

Wasserman   .  . 

Negative  . .  . 

Tuberculin  tests  and  pul- 
monary involvement. 

PROGNOSIS  AND  TREATMENT  OF  LARYNGEAL 
TUBERCULOSIS 

By  Norval  H.  Pierce,  M.D. 
university  op  illinois 

Prognosis  in  cases  of  laryngeal  tuberculosis  depends  on  various  fac- 
tors which,  bear  one  upon  another  in  any  given  case  of  tuberculosis.  In 
case  of  tuberculosis,  infiltration  of  a  limited  area  in  the  larynx,  occur- 
ring in  cases  where  the  lung  is  not  very  much  affected,  which  is  running 
an  afebrile  or  subfebrile  course,  the  prognosis  is  favorable.  In  cases 
where  the  tuberculous  infection  first  occurs  after  the  lung  has  become 
considerably  involved,  where  the  strength  is  greatly  diminished  and 
where  fever  is  continuous  and  high,  the  prognosis  is  invariably  bad.  Not 
only  does  this  bear  on  the  larynx  alone,  but  the  laryngeal  conditions 
react  unfavorably  upon  the  pulmonary  condition  itself.  Patients  will 
not  eat  because  of  the  pain,  would  rather  starve.  This  has  great  influ- 
ence on  the  diminishing  strength  of  the  patient.  Again,  when  the  laryn- 
geal infiltration  produces  stenosis,  the  patient  is  deprived  of  sufficient 
oxygen  thereby. 

It  is  not  infrequent,  however,  to  see  in  cases  of  the  first  class,  where 
the  lungs  are  not  affected  or  not  demonstrably  affected,  or  where  they 
are  very  slightly  affected,  superficial  tuberculous  affections  of  the 
larynx  undergo  spontaneous  recovery. 

Fortunately,  in  this  country  we  do  not  see  as  much  tuberculous 
laryngitis  as  we  see  in  foreign  countries,  especially  in  Vienna.  I  would 
say,  too,  that,  as  a  general  impression,  laryngeal  tuberculosis  in  Amer- 
ica, and  especially  among  Americans,  has  a  much  better  prognosis  than 
in  tuberculosis  as  it  affects  some  European  people.  I  believe  that 
prognosis  in  laryngeal  tuberculosis  of  South  European  individuals  is 
much  worse  than  the  tuberculosis  prognosis  in  a  Northern  German. 
But  why  this  is  so  is  pretty  hard  to  say.  It  is  not  because  of  better 
nutrition.  The  same  thing  may  be  said  about  bone  tuberculosis,  or  any 
bone  inflammation  for  that  matter.  We  do  not  see  in  America  the 
devastating  effect  of  suppurative  involvement  of  the  temporal  bone,  for 
instance,  that  we  see  in  Southern  Germany. 

Pregnancy  has  a  very  unfavorable  effect  on  tuberculosis  of  the  larynx, 
so  that  in  certain  cases  the  question  of  producing  abortion  may  very 
properly  be  considered  and  the  induction  also  of  premature  birth  at  the 
eighth  or  seventh  month  may  also  be  considered  in  a  given  case.  I  remem- 
ber one  woman  who  had  a  Caesarian  section  performed  on  her  while  in 
the  very  last  stages  of  tuberculosis — emaciated,  scarcely  able  to  move. 
The  child  lived  and  the  mother  regained  her  strength  and  weight  and 
was  able  to  return  to  her  duties  at  home.  So  that  a  matter  of  pregnancy 
in  a  case  of  tuberculosis  of  the  larynx  is  one  of  great  importance. 

Considering  the  treatment  of  tuberculosis  of  the  larynx,  it  cannot 

76 


XORVAL   H.    PIEECE^    M.D.  77 

be  confined  to  local  treatment.  Local  treatment  is  perhaps  of  secondary 
importance  to  general  treatment,  and  the  general  treatment,  fortunately, 
I  am  not  expected  to  discuss  in  this  symposium. 

I  believe  that  tuberculosis  of  the  larynx  should  invariably  be  treated 
in  a  sanatorium,  wherever  that  is  possible.  It  is  a  hospital  disease.  It 
is  very  pitiful  to  see  these  patients,  especially  with  advanced  tubercu- 
losis of  the  larynx,  traveling  in  all  kinds  of  weather  from  their  homes 
to  physicians'  offices,  and  gaining  little  or  no  benefit.  Perhaps  it  even 
harms  them  more.  It  is  surprising  to  see  how  these  same  patients,  when 
in  a  sanatorium,  where  special  treatment  is  instituted  and  where  con- 
tinuous observation  can  be  carried  out,  greatly  and  quickly  improve.  I 
do  not  hesitate  to  say  that  tuberculosis  of  the  larynx  should  always  be 
treated  in  a  hospital ;  always  in  a  special  sanatorium,  where  it  is  possible. 

Now  the  treatment  of  tuberculosis '  of  the  larynx  may  be  divided 
into  the  surgical  removal  of  the  diseased  portion  of  the  larynx  and  the 
treatment  of  the  local  suffering,  we  may  say. 

The  most  important  point  in  the  treatment  of  tuberculous  laryn- 
gitis is  non-use  of  the  voice.  Absolute  silence  should  be  enforced  in 
every  case  of  tuberculosis  of  the  larjTix.  This  has  an  enormous  effect 
on  the  healing  process  of  tuberculosis  of  the  larynx.  Patients  should 
not  be  allowed  to  utter  one  word,  at  any  time.  All  the  communication 
with  the  outside  world  should  be  carried  on  by  writing;  not  even  the 
whisper  voice  should  be  allowed.  So  great  a  factor  is  this  in  the  treat- 
ment of  tuberculosis  that  tracheotomy  has  been  recommended,  by  our 
German  confreres  especially.  There  is  no  doubt  that  certain  cases 
would  be  vastly  benefited  by  this  procedure,  but  if  we  are  to  expect  the 
best  results  we  should  select  those  cases  that  are  below  the  age  of  25, 
where  the  larynx  is  extremely  involved,  where  the  lung  is  very  slightly 
involved,  where  the  strength  is  still  preserved  and  where  the  fever  is 
not  high.  If  we  can  also  have  a  fourth  item  in  the  selection,  it  should 
be  done  at  a  season  of  the  year  or  in  a  location  where  the  patient  can 
reside  out-of-doors,  so  that  the  air  taken  into  the  tracheal  opening  shall 
not  irritate.  I  have  seen  cases  of  this  kind  treated  by  tracheotomy 
recover.    They  have  recovered  without  any  other  local  treatment. 

The  surgical  removal  of  the  diseased  portions  of  the  larynx  should 
only  be  attempted,  in  my  opinion,  in  cases  where  the  disease  is  very 
sharply  confined  to  given  localities  in  the  larynx,  especially  in  the  inter- 
arytenoid  region,  and  you  know  this  is  the  point  where  it  most  fre- 
quently occurs.  Where  it  is  sharply  defined,  then  you  may  attempt  to 
remove  by  cutting. 

Suspension  laryngoscopy  opens  a  new  field  in  surgical  treatment  of 
laryngeal  tuberculosis.  By  this  method,  one  can  operate  as  accurately 
and  as  safely  in  the  larynx  as  one  can  on  the  surface  of  the  skin.  These 
growths,  of  course,  can  be  operated  by  the  indirect  method.  This  requires, 
undoubtedly,  very  much  more  training.  I  might  say  that  it  requires 
more  training  than  the  younger  generation  of  laryngologists  is  apt  to 


78  PROGNOSIS    AND    TREATMENT    OF    LARYNGEAL    TUBERCULOSIS 

acquire,  on  account  of  the  advent  of  direct  laryngoscopy.  Where  the 
larynx  is  involved  to  any  extent,  where  there  is  a  voluminous  infiltra- 
tion going  on,  any  attempt  at  removal  is  a  very  great  error.  We  know 
that  the  entire  larynx  has  been  excised  for  tuberculosis  of  the  larynx. 
Usually  it  has  been  done  through  a  mistaken  diagnosis,  tuberculosis 
being  mistaken  for  carcinoma.  However,  there  have  been  cases  where 
known  tuberculosis  of  the  larynx  has  led  to  excision  of  the  larynx  and 
patients  have  invariably  died  within  the  course  of  three  of  four  days 
from  septic  pneumonia,  so  that  the  removal  of  the  larynx  in  tuberculosis 
is  not  considered  at  all  any  more.  Neither  is  laryngofissure,  where  the 
larynx  is  cut  in  the  middle  and  turned  out  and  the  tuberculous  growth 
removed.  Still,  there  have  'been  cases  reported  where  this  operation 
has  been  followed  by  recovery. 

Now,  the  amelioration  of  local  suffering.  That  perhaps  is  the  most 
important  part  of  the  proposition  in  practical  work. 

I  believe  that  it  is  a  great  mistake  to  persist  in  local  applications  ex- 
cept in  selected  cases.  Lactic  acid  does  much  more  harm  than  good  in 
cases  in  the  infiltration  stage — where  there  is  no  breaking  down  of  the 
tuberculous  process.  I  have  known  where  patients  have  gone  over  and 
over  again  to  their  physician  to  have  these  tuberculous  infiltrations 
touched  up  with  75  per  cent,  lactic  acid.  It  does  no  good  surely  and 
the  cough  and  suffering  that  are  engendered  are  very  harmful  to  the 
patient. 

The  effect  of  lactic  acid  on  ulcerations  is,  in  my  opinion,  somewhat 
more  beneficent.  I  will  admit  frankly  that  I  have  never  seen  a  case  of 
tuberculosis  of  the  larynx  cured  by  lactic  acid  alone.  I  have  never  yet 
seen  a  case  cured  by  anything  that  you  might  put  into  the  larynx.  I 
have  seen  cases  recover  from  tuberculosis  of  the  larynx,  but  I  do  not 
know  that  they  could  have  been  traced  to  the  local  application  of  any 
special  medicament. 

I  have  seen  some  cases  benefitted  by  igni-puncture,  as  it  is  called. 
I  have  seen  eases  benefitted  by  amputation  of  the  epiglottis  when  the 
disease  is  limited  to  this  region. 

Sprays  with  creosote  and  menthol  and  what  not  may  be  of  benefit 
in  preventing  or  relieving  irritation  coughs  and  should  always  be  carried 
out,  especially  in  sanatoria.  The  use  of  powders  in  the  larynx  I  am 
somewhat  doubtful  of;  in  fact  any  of  those  powders  that  have  the 
reputation  of  being  anaesthetic  to  the  mucous  membrane  other  than 
cocaine. 

There  is  a  method  of  self -medication,  where  the  patient  puts  a  tube 
into  the  pharynx  with  a  load  of  powder  in  the  tube.  There  is  a  curve  at 
the  back  portion  of  the  tube  which  is  directly  over  the  larynx;  the  pa- 
tient inhales  into  the  tube  and  insufflates  his  own  larynx.  I  have  seen 
more  coughing  and  more  distress  from  this  method  of  treatment  than 
anything  else.  I  am,  therefore,  as  you  can  readily  understand,  radical 
and  very  conservative  regarding  the  treatment  of  the  larynx.    In  cases 


G.  A.   TORRISON,  M.D.  79 

where  the  patient  is  not  much  affected,  the  lung  is  not  much  involved, 
fever  is  not  high  and  where  the  strength  is  still  present  and  the  tuber- 
culosis of  the  larynx  is  localized,  we  should  treat  it  surgically. 

The  best  way  to  control  pain  and  cough  in  these  patients,  in  my 
opinion,  is  injection  in  the  superior  laryngeal  nerves  with  alcohol.  Both 
nerves  can  be  injected  at  the  same  time,  if  necessary. 

Lastly,  I  do  not  hesitate  to  recommend,  when  this  painful  scene  is 
gradually  drawing  to  an  end,  the  abundant  use  of  morphine. 


PROGNOSIS  AND  TREATMENT  IN  LARYNGEAL 

TUBERCULOSIS 

By  G.  a.  Toreison,  M.D. 

CHICAGO 

In  the  first  place,  I  perfectly  agree  with  what  Dr.  Kenyon  has  said 
concerning  the  larynx  in  the  beginning  of  pulmonary  tuberculosis.  In 
almost  all  of  the  cases  there  is  more  or  less  congestion  of  the  larynx. 
If  there  is  general  constitutional  anaemia,  however,  we  wiU.  find  anaemia 
in  the  larynx  but  in  nearly  every  case  we  find  some  congestion  of  the 
larynx  and  especially  in  the  posterior  part  of  the  larynx.  I  agree  with 
Dr.  Kenyon  that  the  congestion  in  a  great  many  cases  is  due  to  talking 
and  to  coughing. 

In  many  cases  of  pulmonary  tuberculosis  there  is,  so  far  as  we 
can  see,  simply  a  laryngitis  present.  It  is  very  hard,  very  often,  to  de- 
termine whether  this  laryngitis  is  catarrhal  or  tuberculous  in  character. 
As  Dr.  Kenyon  has  said,  it  is  very  important  that  the  larynx  be  watched 
in  this  disease  and  that  the  laryngitis  be  relieved,  if  possible,  because 
a  simple  laryngitis  in  the  presence  of  pulmonary  tuberculosis  may  pre- 
dispose to  tuberculous  laryngitis. 

Besides  the  cough,  however,  as  the  cause  of  laryngitis  in  pulmonary 
tuberculosis,  I  believe  the  condition  of  the  nose  plays  an  important  part, 
as  it  does  in  the  production  of  chronic  catarrhal  laryngitis  at  any  time. 
Where  there  is  mouth  breathing  and  obstruction  to  nasal  respiration, 
we  are  much  more  likely  to  find  laryngeal  congestion  than  where  there 
is  a  normal  nose  and  normal  nasal  breathing. 

As  Dr.  Pierce  has  said,  the  prognosis  in  laryngeal  tuberculosis  is  not 
necessarily  grave.  There  are  a  great  many  cases  that  do  recover.  In 
cases  of  slowly  progressing  pulmonary  tuberculosis  the  laryngeal  tuber- 
culosis may  recover,  while  in  the  acutely  progressing  cases  of  pulmonary 
tuberculosis,  in  most  cases  when  the  larynx  becomes  involved,  I  think 
it  is  very  rare  that  patients  recover. 


80  PROGNOSIS   AND    TEEATMENT    OF    LARYNGEAL    TUBERCULOSIS 

The  prognosis,  then,  of  course,  depends  very  much  upon  the  general 
condition  of  the  patient  and  upon  the  progress  of  the  pulmonary  dis- 
ease. If  the  patient  has  good  resistance,  if  the  pulmonary  disease  is  only 
slowly  progressive,  laryngeal  involvement  does  not  necessarily  make  the 
prognosis  absolutely  bad. 

So  far  as  the  treatment  is  concerned,  the  most  important  thing,  as 
Dr.  Pierce  has  pointed  out,  is,  I  believe,  rest.  Kest  of  the  larynx,  rest 
of  the  body  also,  and  rest  of  the  mind.  It  is  impossible  to  get  rest  of 
the  larynx  if  you  allow  your  patient  to  keep  coughing,  and  therefore  one 
of  the  most  important  things  to  control  is  coughing.  It  is  also,  of  course, 
necessary  to  forbid  the  use  of  the  voice.  The  patient  should  be  forbid- 
den to  speak ;  in  fact,  he  should  be  made  to  give  his  larynx  as  much  rest 
as  possible.  The  general  health  should  be  looked  after.  The  more  the 
patient  can  improve  his  general  health,  the  better  it  will  be  for  his 
laryngeal  trouble. 

The  most  distressing  symptom,  as  has  been  said,  in  laryngeal  tubercu- 
losis is  the  pain.  The  pain  interferes  with  nutrition  and  when  a  tuber- 
culous patient's  nutrition  is  interfered  with  he  will  run  down  rapidly. 

The  use  of  sprays  is  valuable,  I  think,  in  some  cases  and  I  think 
surgery  is  valuable  in  some  cases.  There  has  been  a  great  deal  of 
discussion  as  to  the  value  of  surgical  treatment.  I  believe  that  where 
the  laryngeal  tuberculosis  is  localized,  as  Dr.  Pierce  has  said,  surgery 
is  very  often  valuable,  and  particularly  where  there  is  ulceration.  Where 
the  general  condition  of  the  patient  is  fairly  good  and  there  is  a  slowly 
progressing  ulceration,  for  instance  in  the  interarytenoid  regions,  I 
believe  that  form  of  an  ulcer  can  be  made  to  heal  more  rapidly  by  the 
use  of  surgical  measures  than  by  ordinary  medical  treatment,  by  the 
use  of  sprays,  for  instance.  I  think  in  most  cases  it  is  good  practice 
to  punch  out  the  granulations  on  the  face  of  the  ulcer  and  then  apply 
lactic  acid  or  other  remedy.  Lactic  acid  or  any  other,  I  believe,  has 
absolutely  no  value  except  in  cases  of  ulceration,  in  promoting  the  cure 
of  a  laryngeal  tuberculosis,  though  there  are  applications  which  will 
relieve  pain. 

Nasal  Condition.  I  believe  that  in  pulmonary  tuberculosis  and 
laryngeal  tuberculosis,  the  condition  of  the  nose  is  very  important.  It 
is  very  important  to  establish  nasal  respiration.  A  great  many  people, 
not  only  tuberculous  people  but  others  as  well,  have  difficulty  in  breath- 
ing through  the  nose  at  night,  even  though  not  troubled  during  the  day. 
In  all  cases  of  tuberculosis  I  think  that  the  nose  should  be  looked  after 
very  carefully,  as  well  as  the  larynx. 


PREGNANCY  AND  TUBERCULOSIS 

Bt  Chaeles  S.  Bacon,  M.D. 
university  of  illinois 

I  think  Dr.  Sachs  is  exactly  right  in  saying  that  there  is  no  general 
agreement  as  to  the  policy  that  should  be  pursued  in  dealing  with  this 
problem  and  I  think  it  is  true  that  individuals  even  are  not  clear  as 
to  what  they  should  do  in  these  cases.  We  are  studying  the  problem 
still  and  ought  to  look  at  all  sides  and  not  approach  it  with  any  bias, 
one  way  or  the  other. 

For  the  proper  discussion  and  study  of  the  subject,  it  is  necessary 
to  make  use  of  what  data  we  have.  That  is  not  very  extensive  or  in 
detail,  but  by  making  use  of  the  figures  that  are  given  in  the  reports  of 
the  United  States  Census  Bureau  and  comparing  those  with  reports 
from  other  sources  and  making  certain  approximations,  we  may  reach 
certain  data  that  can  be  accepted  for  the  present  as  more  or  less  approxi- 
mately true. 

I  am  going  to  give  figures  for  the  United  States  and  then  reduce 
them  to  Chicago.  Let  me  say  that  the  population  for  the  United  States 
is  one  hundred  million,  which  it  is  or  will  be  in  a  year  or  so.  The  popu- 
lation of  Chicago  is  approximately  one-fortieth  of  that,  or  two  and 
one-half  million.  Now,  taking  the  table  given  in  the  United  States 
Census  Report  of  1909,  which  contains  the  standard  million,  giving  the 
population  at  different  ages,  and  applying  that  to  the  present  condition 
(we  do  not  know  whether  this  is  exactly  true  or  not  because  the  standard 
million  table  of  the  1910  census  has  not  yet  been  made),  we  may  say 
that  there  are  about  twenty-three  million  women  in  the  United  States 
of  child-bearing  age;  that  is,  from  fifteen  to  forty-five  years.  By  the 
way,  I  should  say  that  in  some  papers  previously  written  I  have  given 
figures  that  differ  a  little  from  those  given  today,  because  at  that  time 
I  made  a  computation  on  the  basis  of  the  years  from  twenty  to  fifty. 
It  is  better,  because  of  the  way  the  census  reports  are  made,  to  take  the 
other  years,  and  also  they  are  more  accurate  because  there  are  certainly 
more  women  bearing  children  below  the  age  of  twenty  than  there  are 
above  forty-five. 

Taking  these  ages — fifteen  to  forty-five — and  the  population  data  of 
the  census  of  1900,  we  fijid  that  there  are  twenty-three  million  women 
in  the  United  States  of  child-bearing  age.  Now  the  death  rate  in  the  last 
report,  1913,  is  about  six  per  thousand  for  that  age.  That  means  that  in 
the  United  States  about  138,000  women  die  annually.  This,  of  course, 
is  approximate  because  we  have  the  reports  in  the  census  only  from 
the  Registration  Area,  which  comprises  only  63.3%  of  the  entire  pop- 
ulation of  the  United  States.  By  reducing  the  figures  in  the  report 
to  correspond  with  the  whole  United  States  we  find  that  about  138,000 
women  die  yearly,  making  a  death  rate  of  six  per  thousand,  correspond- 

81 


82  PREGNANCY   AND    TUBERCULOSIS 

ing  to  a  death  rate  of  males  of  that  period  of  7.6  per  thousand.  Now, 
of  these  138,000  women  of  the  child-bearing  age  that  die,  just  about 
40,000  die  of  tuberculosis.  That  makes  the  deaths  from  tuberculosis  29 
per  cent,  of  all  the  deaths  of  that  group,  considerably  over  a  quarter,  as 
you  see,  and  it  makes  a  death  rate  from  tuberculosis  in  that  group  of 
1.7  per  thousand.  That  corresponds  to  the  death  rate  of  males  of  2.1 
per  thousand  and  the  male  tuberculosis  death  rate  is  28  per  cent,  of  the 
total  death  rate  of  that  age  period.  That  is,  there  are  not  quite  the 
same  proportion  of  males  who  die  of  tuberculosis  as  females,  but  there 
are  a  larger  number  because  there  are  a  larger  number  of  deaths  in 
general. 

Now  in  order  to  get  the  next  element — the  number  of  labors  or  the 
number  of  pregnancies — we  would  have  to  have  birth  statistics,  and  we 
have  not  these,  as  you  know.  We  are  practically  at  sea,  and  can  take 
almost  any  multiple  that  we  wish,  but  I  am  inclined  to  think  that  we 
shall  not  go  very  far  astray  when  we  say  there  are  just  about  twenty- 
three  in  a  thousand;  the  pregnancies  number  about  twenty-three  in  a 
thousand  of  the  whole  population.  That  would  mean  that  less  than 
twenty  children  in  a  thousand  are  born  because,  as  everyone  knows, 
there  are  somewhere  from  20  to  25  or  30  per  cent  of  abortions,  and 
certainly  a  birth  rate  of  between  eighteen  and  twenty  in  this  country  is 
not  large.  If  I  say  that  the  pregnancy  rate,  then,  is  twenty-three  per 
thousand  of  population,  we  shall  not  be  very  far  astray.  That  would 
give  us,  then,  about  2,300,000  pregnant  women  in  the  United  States. 

Now,  in  order  to  get  the  frequency  of  tuberculosis,  we  have  got  to 
know,  of  course,  not  only  the  mortality  from  tuberculosis  but  also  the 
length  of  life  after  tuberculosis  occurs,  and  that  has  been  variously  esti- 
mated. I  formerly  took  the  figure  five  as  the  multiple  or  frequency  coef- 
ficient, multiplying  the  mortality  by  five  to  get  the  frequency  and  that  is 
also  the  multiple  that  was  taken,  I  noticed  a  year  or  two  ago,  by  Dr. 
Unterberger  in  Stuttgaart.  I  think  that  is  rather  low,  especially  nowadays 
when  the  diagnosis  of  tuberculosis  is  much  more  exact,  and  I  think  that 
eight  is  nearer  the  proper  number.  So  we  would  say  that  if  forty  thous- 
sand  women  die  annually  of  tuberculosis  (when  I  say  women  I  mean 
women  of  child-bearing  age),  then  there  will  be  from  200,000  to  320,000 
(more  nearly  320,000)  tuberculous  women  in  the  United  States,  and  if 
one-tenth  of  them  are  pregnant  (because,  as  we  know,  there  is  nothing 
in  tuberculosis  that  particularly  prevents  pregnancy),  then  we  would 
say  that  there  are  every  year  from  twenty  thousand  to  thirty-two  thou- 
sand tuberculous  women  pregnant  in  the  United  States. 

The  other  factor  that  we  have  to  consider  is  that  of  mortality  of 
children,  and  I  say  the  mortality  of  children  under  five  years  of  age, 
because  a  child  is  with  its  mother  most  of  the  time  for  the  first  five  years 
and  probably  gets  its  infection  from  the  mother.  As  you  know,  the 
mortality  is  not  great  among  children  under  five  years.  About  ten  thou- 
sand children  under  five  die  annually  in  the  United  States. 


CHAELES   S.   BACON,   M.D.  83 

Reducing  these  numbers  to  find  the  Chicago  data,  we  should  have, 
with  a  population  of  about  one-fortieth  of  the  United  States,  about  eight 
hundred  tuberculous  women  pregnant  in  Chicago  in  a  year,  and  that 
would  correspond  to  somewhere  between  fifty-six  to  sixty  thousand 
pregnancies  in  Chicago.  You  know,  of  course,  in  the  last  year  or  two, 
since  the  birth  certificates  are  paid,  over  forty-two  to  forty-three  thou- 
sand were  reported  in  a  year.  I  think  that  corresponds  pretty  well. 
With  fifty-six  to  sixty  thousand  pregnancies  here,  there  will  be  about 
eight  hundred  tuberculous  women  pregnant  and  about  two  hundred  and 
fifty  children  under  five  years  who  die  of  tuberculosis. 

Now  to  consider  the  question  of  the  effect  of  pregnancy  on  tubercu- 
losis. Here  we  come  upon  two  entirely  different  views.  Years  ago  the 
opinion  was  held  by  some  that  tuberculosis  improves  during  pregnancy 
and  that  agrees  with  the  experiences  of  a  great  many  of  us  today.  We 
know  that  frequently  if  a  woman  gets  through  the  hard  second  and 
third  months  well,  she  may  increase  in  weight  and  her  tuberculosis 
seem  to  improve  during  pregnancy.  It  has  been  noted,  however,  by 
everyone,  that  in  the  puerperal  period  the  women  often  run  down  and 
sometimes  those  who  have  begun  badly  continue  to  run  down  during 
their  pregnancy.  Now  opinions,  I  say,  differ  as  to  the  effect  in  general. 
Some,  basing  their  conclusions  on  their  own  personal  experiences  in  hos- 
pitals, find  that  pregnancy  is  always  a  very  serious  complication  of 
tuberculosis.  Why  pregnancy  should  be  a  serious  complication  I  will 
not  discuss,  except  to  say  that  the  theories  that  chemical  changes  in  the 
blood  affect  the  tuberculous  development  are  as  yet  only  theories.  One 
reason  given  for  the  increase  of  the  tuberculous  process  in  the  early 
puerperium  is  that  many  of  the  latent  tuberculous  foci  break  down 
during  labor. 

Detailed  mortality  statistics  of  tuberculous  puerpera  are  not 
numerous.  One  of  the  best  reports  I  have  seen  was  by  Dr.  Catherine 
Van  Tuessenbroeck,  of  Holland,  who  compiled  the  statistics  of  the  four 
largest  cities  of  Holland  and  made  a  very  careful  analysis,  and  she  found 
this  to  be  true, — that  the  mortality  in  the  puerperal  period  was  increased 
in  the  first  six  months  and  considerably  decreased  after  the  first  six 
months.  Dividing  the  first  year  into  halves,  for  the  first  six  months 
there  was  an  increase  in  mortality,  and  decrease  in  the  second  six  months, 
so  that  there  was  not  a  great  change  in  the  general  mortality  in  the 
year.  That  is  a  rather  astonishing  fact  but  her  figures  seem  to  prove 
it  without  a  doubt.  At  any  rate,  it  shows  that  this  question  is  not 
settled.  It  shows  what  we  all  know, — that  women  often  do  run  down 
right  after  labor.  But  that  there  is  very  marked  increase  in  the  death 
rate  is  not  quite  certain. 

I  think  that  the  difference  in  the  treatment  of  pregnant  women  and 
also  of  women  in  labor  and  in  the  puerperal  period  has  very  much  to 
do  with  the  death  rate.  If  women  are  treated  as  they  were  twenty  or 
thirty  years  ago,  kept  away  from  the  air,  not  properly  fed,  they  prob- 


84  PREGNANCY   AND   TUBERCULOSIS 

ably  will  show  many  more  signs  of  increase  in  the  tuberculous  process 
during  the  pregnancy.  If  the  labor  is  conducted  in  such  a  way  that 
they  get  some  genital  wound  infection  and  later  they  are  kept  housed, 
kept  away  from  the  air  and  not  fed  properly,  they  will  run  down  and 
undoubtedly  pregnancy  and  labor  would  have  a  very  serious  effect.  On 
the  other  hand,  if  the  patient  can  be  kept  in  ideal  condition  during 
the  pregnancy,  if  the  labor  can  be  conducted  ideally  and  if  the  woman 
can  be  kept  in  ideal  condition  afterwards,  I  believe  that  we  shall  find 
that  there  is  not  as  great  danger  from  pregnancy  to  the  tuberculous 
woman  as  we  have  sometimes  thought. 

Now  another  thing  is  to  be  thought  of,  and  that  is  the  effect  on  the 
child.  We  have  seen  that  the  number  of  deaths  from  tuberculosis  in  the 
first  years  of  life  is  small,  but  still  we  have  approximately  250  deaths 
in  Chicago,  with  perhaps  eight  hundred  tuberculous  pregnant  women, 
and  it  may  be  that  most  of  these  are  from  that  class.  This  is  an  item 
not  to  be  overlooked  and  in  my  mind  is  very  important.  Infant  tuber- 
culosis, we  are  agreed,  is  due  chiefly  to  infection  of  the  child  after 
birth,  although  recent  observations  have  shown  occasionally  that  there 
has  been  placental  infection  and  that  the  child  may  be  infected  in  the 
uterus.  That  does  not  happen  very  often.  The  chief  thing  is  infection 
after  birth. 

Now  comes  the  question  of  Prevention  of  Pregnancy.  Undoubtedly 
we  agree  that  a  tuberculous  woman  should  not  become  pregnant.  If 
a  girl  is  tuberculous  she  should  not  marry,  and  that  should  be  insisted 
upon  over  and  over  again.  The  question  wiU  arise :  How  long  after 
the  cure  can  she  marry  and  risk  a  pregnancy?  "We  had  better  say 
two  years  after  the  cure  is  complete.  That  is,  however,  the  shortest 
period.  With  the  married  women  we  would  advise  that  they  do  not 
become  pregnant,  and  this  advice  is  to  be  supplemented  with  the  best 
instructions  that  we  can  give.  The  question,  however,  comes  up  of 
sterilization  to  prevent  pregnancy  and  that,  in  some  cases,  is  to  my  mind 
justifiable,  especially  where  the  patient  has  no  great  degree  of  intelli- 
gence and  where  she  has  perhaps  several  living  children.  The  only  way 
to  certainly  prevent  further  pregnancy  is  by  sterilization,  which  can 
be  done  with  a  tubal  excision  operation  or  with  the  X-ray. 

If  the  woman  becomes  pregnant,  should  abortion  te  induced? 

You  have  gathered  from  what  I  have  already  said,  that  I  should  not 
favor  that  very  strongly.  It  certainly  should  not  be  the  general  rule, 
because  of  several  reasons.  One  is  this:  the  results  of  abortion  are  not 
very  good.  There  are  two  indications — prophylactic  and  vital — for 
abortion  to  prevent  further  trouble,  and  to  save  the  woman's  life.  The 
vital  indication  is  worthless.  If  the  woman  is  in  such  condition  that 
she  is  pretty  sure  to  die  if  she  goes  on  with  pregnancy,  she  will  be 
pretty  sure  to  die  after  abortion  is  induced,  so  that  it  is  not  really 
a  reasonable  indication.    Possibly  we  want  to  save  her  to  her  family  a 


CHARLES   S.    BACON,    M.D.  85 

little  longer,  but  most  authorities  agree  that  the  women  go  down  pretty 
nearly  as  fast  after  the  operation  as  without  it. 

The  prophylactic  indication  is  the  prevention  of  further  increase  of 
trouble  in  a  woman  that  has  a  good  hope  of  success  in  her  fight  with 
tuberculosis.  Before  deciding  on  this  indication  it  is  necessary  to  answer 
the  question:  How  can  the  pregnancy  be  managed?  Can  the  patient 
be  treated  in  her  home  or  sanatorium  properly?  If  she  can  be  sent  to 
a  sanatorium  like  our  new  Sanatorium  and  be  cared  for  in  an  ideal  way 
during  her  pregnancy,  and  the  labor  conducted  in  a  proper  way,  the 
child  taken  from  her  and  properly  cared  for,  if  that  can  be  done  I 
believe  it  is  very  much  better  than  induction  of  abortion.  It  could  not 
be  done  until  our  Sanatorium  was  opened,  because  there  was  no  institu- 
tion where  the  patients  could  go. 

I  should  say  that  it  is  very  seldom  that  induction  of  abortion  is 
indicated.  I  think  it  will  grow  less  and  less  as  we  can  improve  our  man- 
agement. 

There  is  another  thing  I  just  want  to  say  a  word  about — that  it  is  a 
bad  thing  socially  and  morally.  It  is  letting  down  the  bars;  it  becomes 
an  excuse  for  all  sorts  of  practitioners  to  induce  abortion,  claiming  that 
it  is  for  tuberculosis. 

Now  I  think  I  have  indicated  in  what  I  have  said  what  I  believe 
is  the  proper  way  to  manage  these  cases.  Care  for  them  as  you  would 
for  other  tuberculous  patients  in  the  Sanatorium  or  at  home  if  you  can 
get  the  same  care  as  at  the  Sanatorium.  The  Chicago  Municipal  Tuber- 
culosis Sanitarium  has  provided,  as  you  all  know,  the  essentials  for  car- 
rying out  this  treatment.  The  essential  things  are  the  nursery  and  the 
confinement  room.  The  nursery  where  the  baby  is  put  after  birth  is 
protected  from  the  corridor  with  a  glass  partition.  The  mothers  do  not 
get  to  the  babies  at  all,  never  go  into  the  nursery.  They  can  see  their 
babies  through  the  partition  and  see  how  they  are  doing. 

Babies  are  to  be  fed  with  milk  or  possibly  may  use  mother 's  milk  that 
is  expressed  or  pumped  from  the  breast.  I  think  it  will  be  a  very 
interesting  investigation  to  discover  whether  mother's  milk  is  safe  for 
the  babies.  If  a  certain  amount  can  be  given,  without  injury  to  the 
mother,  it  may  be  desirable  to  give  it. 

The  women,  as  soon  as  they  are  able,  are  taken  away  from  the  hospital 
and  put  into  the  cottages  again,  and  can  stay  there  for  two  or  three 
months,  and  the  baby  stays  in  the  nursery  as  long  as  necessary. 

This  institution  provides  for  twenty  babies.  If  babies  remain  for 
three  months,  as  they  certainly  ought  to,  provision  is  made  for  eighty 
patients  in  a  year  and  that  is  my  estimate  as  to  the  number  of  cases 
you  will  have  after  you  get  running,  eighty  cases  in  the  course  of  a 
year.  That  can  be  increased,  if  the  demand  increases,  as  it  probably 
will,  by  increasing  the  size  of  the  nursery.     "We  have  got  the  confine- 


86  PREGNANCY   AND   TUBERCULOSIS 

ment  room  and  other  provisions.  It  has  not  been  expensive  and  I  beKeve 
the  establishment  of  the  maternity  department  is  the  most  far-reaching 
improvement  in  the  control  of  this  important  source  of  infection. 


PREGNANCY  AND  TUBERCULOSIS 
By  Joseph  B.  DeLee,  M.D. 

CHICAGO 

I  believe  that  I  am  responsible,  indirectly,  for  this  meeting,  or 
rather  for  the  adoption  of  this  subject  for  the  meeting.  Some  months 
ago,  while  I  was  revising  my  book,  I  came  to  the  chapter  on  "Tubercu- 
losis and  Pregnancy,"  and  after  reading  over  my  own  production,  I 
realized  how  little  I  knew  about  the  subject.  Happening  to  meet  Dr. 
Sachs  here  in  the  corridor,  I  started  to  quiz  him,  believing  that  the  larger 
store  of  information  is  not  with  the  obstetrician  but  with  the  special 
practitioner  in  tuberculosis.  I  feel,  therefore,  that  Dr.  Sachs  was  very 
unfortunate  in  picking  out  the  speakers  for  this  meeting,  at  least  as  far 
as  I  am  concerned,  because  I  have  very  little  information  to  give  you. 
I  would  much  prefer  to  get  instruction  from  Dr.  Sachs  and  from  you 
all.  If  you  will  stop  to  think  for  a  minute,  you  will  see  that  the 
obstetrician  seldom  devotes  much  time  to  that  subject,  and  a  man  in 
my  position  could  not  give  you  information  on  tuberculosis  in  pregnancy 
because  he  would  look  at  it  from  the  obstetrician's  point  of  view.  Cases 
are  referred  to  him  for  operation  and  in  many  instances  he  receives  a 
letter  something  like  this : 

"Dear  Doctor:    Mrs.  So-and-So  has  tuberculosis.    I  am  send- 
ing her  to  you  for  induction  of  abortion. ' ' 

In  other  words,  the  family  doctor  has  already  made  up  his  mind 
as  to  what  is  to  be  done  and  sends  the  case  to  me  for  operative  pro- 
cedure. 

I  did  have,  years  ago  however,  considerable  personal  experience  with 
the  cases  during  pregnancy  and  afterwards.  And  the  impressions  which 
I  got  in  those  days  are  largely  responsible  for  the  opinions  which  I  still 
hold. 

I  will  briefly  mention  some  of  the  experiences  which  I  had  when  I 
did  have  these  cases  during  pregnancy  and  after  labor.  I  do  not  think 
that  these  women  do  well  during  pregnancy.  In  those  days  we  roughly 
divided  them  into  two  classes :  the  old  chronic  tuberculosis,  usually  in 
middle-aged  women  or  rather  older  women;  and  acute  tuberculosis, 
usually  in  the  newly  married  women  or  women  that  had  been  married 


JOSEPH   B.    DELEE,    M.D.  87 

six,  eight  to  ten  years.  Of  course  that  was  not  arbitrary  at  all,  but  the 
women  seemed  to  fall  in  that  way.  I  delivered  a  great  many  tuberculous 
women  who  had  hemorrhages,  sweats  and  evening  temperature,  had  all 
the  signs  of  chronic  tuberculosis,  some  with  cavities  forming,  who  got 
well  and  nursed  the  babies  in  spite  of  injunctions,  and  passed  out  of 
my  observation,  very  little  the  worse  for  their  experience.  On  the 
other  hand,  I  got  to  look  upon  the  young  women,  pregnant  with  the 
first  child,  who  came  in  with  a  slight  cough,  slight  evening  temperature, 
ruddy  cheeks  and  all  appearances  of  health  with  suspicion  because  I 
found  that  at  the  end  of  the  pregnancy  they  would  lose  their  ruddy 
cheeks,  that  they  stood  labor  poorly  and  went  down. 

So  I  got  the  impression  that  the  younger  women  were  bad  subjects 
and  older  women  the  better  subjects.  I  have  always  had  an  antipathy 
for  statistics,  figures  and  percentages.  First,  my  antipathy  was  due  to 
laziness  in  collecting;  and,  second,  it  was  born  of  distrust.  I  could 
not  trust  the  figures,  because  I  noticed  that  one  man  could  take  the 
figures  and  make  beautiful  deductions,  and  another  could  take  the 
same  figures  and  make  altogether  different  deductions,  so  that  the  figures 
were  not  worth  the  labor  spent  to  obtain  them.  I  have  gotten  to  look 
upon  the  opinion  of  the  man  as  more  valuable  than  statistics.  I  would 
rather  take  Dr.  Bacon's  opinion  than  his  statistics.  In  sizing  up,  there- 
fore, the  value  of  an  opinion,  you  must  take  the  value  of  the  man  into 
consideration.  If  he  is  honest  with  himself,  has  a  logical  mind  and 
experience  in  practice,  then  his  opinion  is  worth  something.  My 
opinions,  therefore,  regarding  tuberculosis,  stand  on  their  merits,  and 
you  can  put  your  own  value  on  them. 

Within  the  last  eight  or  ten  years  I  have  not  followed  tuberculosis 
cases  during  pregnancy  or  afterwards.  If  a  woman  comes  to  me  with 
tuberculosis,  I  have  always  aborted  her  or  turned  to  her  family  physi- 
cian, and  in  the  eases  that  have  been  referred  to  me  explicitly  for  abor- 
tion, I  have  usually  performed  that  operation.  After  delivery  they  dis- 
appear. They  go  back  to  their  family  physicians  and  unfortunately  I 
have  not  taken  the  trouble  to  look  them  up  and  see  what  became  of  those 
particular  patients  subsequently. 

Now  it  might  interest  you,  in  line  with  Dr.  Bacon's  remarks,  if  I 
read  this  article,  which  is  rather  opposed  to  the  position  I  take.  This 
abstract  was  taken  from  the  Journal  of  the  American  Medical  Associa- 
tion and  I  forgot  to  cut  off  the  top  of  the  page  showing  the  name  of  the 
doctor,  but  he  is  a  Hollander. — Pregnancy  and  Pulmonary  Tuberculosis. 

"This  article  is  a  brief  summary  of  the  data  supplied  by  155  physi- 
cians in  the  Netherlands  who  filled  out  question-blanks  asking  for  their 
experience  with  regard  to  the  influence  of  a  pregnancy  on  pulmonary 
tuberculosis.  The  detailed  report  is  to  be  published  in  full  in  a  Dutch 
gynecologic  journal  and  it  is  announced  that  a  reprint  will  be  sent 
on  request  to  Professor  B.  J.  Kouwer,  Utrecht.  Among  the  question- 
blanks  filled  out  and  returned,  54  physicians  reported  constantly  unfav- 


»»  PREGNANCY   AND    TUBERCULOSIS 

orable  experience  and  27  exclusively  favorable.  In  the  35  cases  of 
laryngeal  tuberculosis,  10  of  the  women  survived  with  the  pregnancy 
carried  to  normal  delivery,  and  of  the  children  of  the  25  women  with 
severe  laryngeal  tuberculosis,  seven  are  living. 

' '  Of  the  total  407  cases  of  pregnancy  in  tuberculous  women,  the  dis- 
ease is  said  to  have  been  aggravated  in  184,  while  no  harmful  influence 
was  apparent  in  223  cases.  In  192  cases  the  tuberculous  women  passed 
through  more  than  one  pregnancy ;  56  of  them  died  of  their  tuberculosis. 
Among  these,  one-fifth  succumbed  to  acute  miliary  tuberculosis  and 
one-ninth  in  the  fortnight  after  delivery.  Many  of  the  women  passed 
comparatively  unharmed  through  various  complications  of  the  preg- 
nancy, uncontrollable  vomiting,  hydramnion,  pregnancy  nephritis,  pre- 
mature separation  of  the  placenta,  puerperal  fever,  etc.,  revealing  remark- 
able resisting  powers. 

''On  the  whole,  the  results  of  the  inquiry  justify  a  stand  against  the 
prevailing  pessimism  in  regard  to  the  influence  of  pregnancy  on  pul- 
monary tuberculosis.  The  pregnant  tuberculous  woman  needs,  of  course, 
good  care,  repose,  nourishing  food,  etc." 

My  early  experiences  were  a  little  opposed  to  that,  because  I  found 
that  if  early  in  pregnancy  the  women  were  tuberculous  they  went  doMm 
very  rapidly  and  I  unhesitatingly  recommended  a  therapeutic  abortion. 

This  brings  me  to  the  indications  for  abortion,  in  tuberculosis.  You 
see,  I  will  attack  the  subject  from  a  little  different  angle  than  Dr. 
Bacon.  He  gave  you  the  treatment  of  tuberculosis,  and  I  will  take  up 
the  point  of  indication  for  abortion. 

I  have  recommended  abortion  in  cases  where  there  has  been  a  severe 
degree  of  anaemia.  Some  tuberculous  women,  especially  those  be- 
tween seventeen  and  twenty-one,  and  especially  if  they  are  chlorotic, 
if  pregnancy  comes  on,  develop  a  high  degree  of  anaemia  and  in  these 
women  I  have  leaned  towards  the  interruption  of  pregnancy.  Then,  if 
the  woman  was  the  mother  of  a  large  family  and  developed  acute 
tuberculosis,  I  have  not  hesitated  long  in  emptying  the  uterus.  If  the 
woman  has  hyperemesis  gravidarum,  there  is  another  indication  which 
would  favor  immediate  emptying  of  the  uterus. 

If  the  woman  has  frequent  hemorrhages  early  in  pregnancy,  I  con- 
sider that  a  strong  indication.  When  a  woman  loses  weight  rapidly, 
has  advancing  cavitation  and  a  large  number  of  tubercle  bacilli  in  the 
sputum — in  other  words,  a  rapidly  advancing  tuberculosis — I  find  it 
best  to  induce  abortion. 

If  the  woman  has  just  been  married  and  comes  very  early  in  her 
pregnancy,  with  beginning  tuberculosis,  I  have  induced  abortion,  even  if 
I  thought  she  could  carry  through.  I  wanted  her  to  go  away  and 
devote  all  her  time  to  getting  well,  all  her  strength  and  power  to  getting 
well,  with  the  understanding  that  two  or  three  years  (I  usually  say 
three  years)  after  the  cure  has  been  announced  by  the  family  physician 
she  may  become  pregnant,  because  then  she  can  go  through  it  safely, 
not  once,  but  several  times. 


JOSEPH   B.    DE  LEE,    M.D,  89 

I  have  felt  that  the  fight  against  tuberculosis  is  a  serious  and 
momentous  one.  It  requires  mental  and  physical  stamina.  It  requires 
an  intention  to  get  well,  and  you  all  know  that  a  great  many  cures  of 
tuberculosis  are  interrupted  by  the  fact  that  the  man  gives  up  the 
fight.  A  woman  in  the  pregnant  condition  is  more  likely  to  give  up 
the  fight,  so  I  have  felt  that  if  I  could  relieve  her  of  all  barriers  so  that 
she  is  perfectly  free  to  fight  the  tuberculosis,  she  stands  a  much  better 
show  of  getting  well. 

In  tuberculosis  of  the  larynx  I  consider  it  justifiable  to  empty  the 
uterus. 

The  moral  aspect  of  interference  with  pregnancy  is  an  enormous 
subject  and  in  these  few  minutes  I  would  not  attempt  to  discuss  it  fully. 
No  one  can  disagree  with  Dr.  Bacon  that  the  moral  aspects  of  abortion 
are  too  much  neglected,  and  without  question  abortion  is  done  too  often. 
Whether  or  not  it  is  morally  right  to  kill  a  baby  to  save  the  mother  or 
to  prolong  her  life  or  to  give  her  a  better  chance  to  fight  disease,  as  I' 
just  intimated,  I  am  going  to  leave  to  the  moralists  to  decide.  I  have 
gotten  a  great  deal  of  solace  and  a  great  deal  of  strength  out  of  an  old 
rule  which  was  formulated,  I  think,  first  by  Confucius  and  later  by  an- 
other whom  you  are  all  familiar  with,  namely,  "Do  unto  others  as  you 
would  have  them  do  unto  you,"  and  I  feel  that  if  I  were  a  woman  and 
if  the  question  of  tuberculosis  and  pregnancy  arose,  knowing  as  much 
as  I  do  now,  I  would  certainly  want  every  possible  barrier  against  my 
opportunity  to  struggle  for  continued  existence  removed.  I  believe  that 
is  a  pretty  safe  course  of  practice. 

The  Catholic  church,  as  you  know,  absolutely  forbids  anything  of  this 
kind,  and  I  know,  too,  that  in  several  cases  where  I  have  recommended 
abortion  the  Catholic  priest  has  forbidden  it.  The  women  have  lived  and 
the  babies  were  paraded  before  me  to  make  me  ashamed  of  my  recom- 
mendation. Of  course  I  did  not  follow  these  cases  up,  and  do  not 
know  what  the  end  was,  but  judging  from  experience  I  can  guess. 

Dr.  Jaggard,  whom  you  all  know,  said :  "If  you  want  a  large  num- 
ber of  babies  from  that  particular  woman,  abort  her  and  get  her  per- 
fectly cured  of  the  tuberculosis,  and  then  let  her  bear  children  if  cured. ' ' 

Another  indication  for  abortion  is  kyphosis.  In  those  cases  it  is 
better  to  empty  the  uterus  because  the  lung  capacity  is  already  compro- 
mised and  the  tuberculosis  makes  rapid  progress. 

In  intestinal  tuberculosis  pregnancy  is  very  rare  and  one  should  be 
governed  by  the  symptoms.  If  the  woman  became  pregnant,  I  do  not 
believe  an  abortion  would  be  strongly  indicated. 

If  you  do  decide  to  abort,  what  method  should  he  used,  and  how  are 
you  going  to  do  it  ?  I  recommend  that  tuberculous  cases  be  not  given 
an  anaesthetic.  I  have  found  that  ether  anesthesia  and  others,  including 
gas,  are  very  poorly  borne  by  tuberculous  women.  They  get  inhalation 
general  tuberculosis.  I  do  not  know  whether  anyone  has  had  that  expe- 
rience.   The  mucus  is  breathed  up  and  down  and  infects  new  portions  of 


90  PREGNANCY   AND   TUBERCULOSIS 

the  lungs  and  spots  of  tuberculosis  occur  all  over  the  lungs.  I  have 
found,  too,  that  in  a  few  cases  they  have  gotten  a  pneumonia  from 
which  they  have  recovered  very  slowly,  due  possibly,  or  probably,  to 
the  anaesthetic.  This  clouds  the  prognosis  for  abortion  and  when  you 
are  advising  abortion  for  tuberculous  women  you  have  got  to  take  that 
into  consideration, — will  the  method  of  cure  kill  the  patient?  Abortion 
should  be  done  in  these  cases  without  an  anaesthetic  if  possible,  in  two 
stages,  and  very  often  one  may,  by  injecting  a  one-half  of  one  per  cent, 
novacain  solution  in  the  fornices,  operate  absolutely  painlessly. 

Now  should  you  sterilize  the  woman?  That  depends.  If  you  want 
to  sterilize  the  woman,  you  have  got  to  consider  a  great  many  factors. 
It  is  the  most  ugly  and  disagreeable  operation  for  a  man  to  do  an 
abortion  a  second  time  on  a  woman.  I  will  do  an  abortion  once  and 
empty  the  uterus  and  get  her  free.  If  she  disregards  injunctions  and 
gets  pregnant  again,  I  feel  I  should  not  be  asked  to  repeat  the  abortion. 
You  might  say  that  if  the  first  is  justifiable,  why  not  the  second?  I 
detest  the  second  abortion  for  any  purpose,  and  I  wiU  never  do  it,  nor 
will  I  do  a  craniotomy  a  second  time.  Nowadays  craniotomy  is  a  rare 
operation  and  if  it  does  have  to  be  performed  the  woman  is  warned 
to  consult  expert  skill  early  in  pregnancy  so  that  a  timely  Cesarean  sec- 
tion may  be  done. 

In  sterilizing  a  woman,  should  you  take  off  the  tubes?  That  is  the 
safest  and  quickest  way  of  sterilization  as  far  as  life  is  concerned. 
Take  off  her  ovaries?  It  has  been  found  that  a  woman  who  has  been 
castrated  takes  on  fat  and  that  is  believed  to  prevent  the  increase  of 
tuberculosis.     I  have  seen  women  that  were  fat  and  very  tuberculous. 

Should  you  take  off  the  uterus  to  stop  the  menstrual  flow  and  con- 
serve her  strength  in  that  way?  On  the  other  hand,  the  danger  of 
hysterectomy  is  entirely  underestimated  and  in  individual  cases  you 
will  have  to  balance  those  things  very  carefuUy. 

There  are  three  schools  as  far  as  abortion  in  tuberculosis  is  con- 
cerned. The  first  school  says,  "Abort  every  woman  that  has  tubercu- 
losis. ' '  The  second  school  says,  ' '  Abort  no  woman  who  has  tuberculosis. 
Give  her  aU  kinds  of  treatment  and  let  her  go  through  her  pregnancy." 
The  third  school  says,  "Every  case  must  be  treated  individually."  Put 
me  in  the  third  school. 

When  are  you  going  to  induce  abortion?  You  have  got  to  make  up 
your  mind  right  then.  You  cannot  wait.  Sometimes,  however,  if  you 
get  a  case  where  a  woman  is  five  and  one-half  months  pregnant,  and  you 
can  tide  her  over  six  or  eight  weeks  until  the  child  is  viable,  I  would 
consider  this  justifiable. 

When  labor  comes  on  we  have  to  adopt  a  method  of  delivery  which 
will  reduce  strain  upon  the  lungs  and  heart.  As  soon  as  dilatation 
is  complete,  the  forceps  should  be  applied  to  obviate  the  bearing  down 
effects  which  might  provoke  a  hemorrhage  or  disseminate  tuberculous 
pus. 


JOSEPH    B.    DE  LEE,    M.D.  91 

In  the  puerperal  period  the  patients  have  to  be  watched  with  exceed- 
ing care,  although  we  cannot  do  much  to  prevent  the  complications 
which  are  going  to  arise.  We  cannot  stop  a  miliary  tuberculosis,  but 
we  might  make  the  diagnosis  and  make  sure  that  she  does  not  have  a 
puerperal  infection,  and  treat  her  for  that,  when  as  a  matter  of  fact 
she  is  suffering  from  tuberculosis.  Women  very  often  after  delivery 
have  chills,  fever,  etc.,  which  are  due  entirely  to  tuberculosis  and  not  to 
puerperal  infection. 

Should  a  woman  nurse  her  haby?  I  have  allowed  tuberculous  women 
to  nurse  their  babies  and  I  have  always  found  it  to  be  without  injury 
to  either.  I  have  insisted,  however,  that  the  baby  be  kept  separate  from 
the  mother  except  when  nursing.  I  let  them  nurse  simply  because  I 
found  that  it  was  impossible  to  get  my  desires  carried  out  in  the  matter. 
If  a  woman  is  well-to-do  she  can  employ  a  wet  nurse.  But  most 
families  in  which  this  question  has  arisen  have  not  the  means.  So  the 
baby  has  to  be  nursed,  as  in  many  cases  the  bottle-fed  baby  would  die 
while  the  mother  was  busy  taking  care  of  her  own  health. 

Whether  or  not  a  tuberculous  woman  supplies  tuberculous  milk  I 
do  not  know.  If  the  milk  is  pumped  and  then  fed  to  the  baby,  and 
there  were  any  question  about  it,  you  might  pasteurize  the  milk.  This 
is  under  consideration,  but,  as  I  said,  these  questions  very  seldom  come 
up  to  me,  and  I  had  hoped  that  in  the  general  discussion  I  might  learn 
more  about  them. 


CLINICAL  SYMPTOMS  AND  PHYSICAL  SIGNS  IN  EAELY 
DIAGNOSIS  OF  TUBERCULOSIS 

By  F.  M.  Pottenger,  M.D. 
monrovia,  california 

I  wish  to  thank  your  worthy  President  for  the  privilege  and  honor 
of  addressing  the  members  of  the  Eobert  Koch  Society  today.  I  have 
chosen  as  my  theme  the  clinical  symptoms  and  physical  signs  in  the 
early  diagnosis  of  tuberculosis,  and  shall  discuss  them  from  the  stand- 
point of  their  etiology  and  their  relationship  to  one  another. 

In  studying  the  clinical  history  and  symptom-complex  of  pulmonary 
tuberculosis,  everyone  must  have  been  more  or  less  impressed  with  the 
indefiniteness  of  the  symptoms  and  signs  connected  with  this  disease.  It 
is  my  purpose  today  to  try  to  bring  some  order  out  of  this  chaos. 

There  are  some  twenty-five  or  thirty  different  symptoms  which  accom- 
pany early  tuberculosis,  and  even  more  in  advanced  tuberculosis;  and, 
if  we  think  of  each  symptom  as  an  individual  entity,  there  is  no  end  of 
confusion.  By  carefully  studying  these  various  symptoms  I  have  found 
that  they  all  belong  to  three  groups,  according  to  their  etiology  and  I 
offer  this  classification  to  you  today.  I  published  this  first  some  two 
years  ago  ("Some  Practical  Points  in  the  Diagnosis  of  Active  Tubercu- 
losis," Northwest  Medicine,  January,  1914),  but  I  can  see  even  more 
clearly  than  I  did  at  that  time  the  great  value  of  this  etiological  study, 
and  I  trust  that  this  classification  may  be  of  great  value  to  you  who 
are  working  so  closely  in  the  early  diagnosis  of  this  disease. 

The  classification  which  I  offer  is  as  follows:  (1)  Those  due  to 
toxemia;  (2)  those  due  to  reflex  action;  and  (3)  those  due  to  the  tuber- 
culous process  per  se : 

GROUP  II 


GROUP  I 
Toxemia 
Malaise 

Lack  of  endurance 
Loss  of  strength 
Lack  of  appetite 
Nervous    instability 
Digestive  disturbances 
Loss  of  weight 
Eapid  pulse 
Night  sweats 
Temperature 
Anemia 


Eeflex   origin 

Hoarseness 

Tickling  in  larynx 

Cough 

Digestive  disturbances 

Circulatory  disturbances 

Loss  of  weight 

Chest   and  shoulder  pains 

Flushing  of  face 

Apparent    anemia 


GROUP  in 
Tuberculous    involvement 

per  se. 
Frequent    and    protracted 

colds 
Spitting  of  blood 
Pleurisy 
Sputum 
Temperature 


It  is  characteristic  of  the  symptoms  of  tuberculosis  that  they  are 
inconstant.  We  do  not  find  any  single  symptom  or  any  particular  group 
of  symptoms  present  under  all  circumstances.  The  explanation  of  this 
fact  is  plain  when  we  study  the  symptoms  according  to  their  respective 
groupings. 

The  symptoms  which  are  best  known  fall  in  Group  1 — those  due  to 


92 


F.    M.    POTTENGER,    M.D.  93 

toxemia.  It  will  be  noticed  that  these  are  widespread  in  their  expression, 
involving  many  different  organs  and  parts.  Aside  from  the  anemia  and 
rise  of  temperature,  these  all  point  to  a  disturbance  on  the  part  of  the 
sympathetic  nervous  system.  Further  observation  will  show  that  this 
group  of  symptoms  is  present  only  under  two  conditions:  first,  during 
periods  when  the  disease  is  definitely  active  and  toxins  are  being  thrown 
into  the  blood  stream;  and,  second,  when  the  disease  is  not  particularly 
active  but  auto-inoculation  is  causing  toxemia  to  be  kept  up  by  over- 
exertion, wrong  habits  of  living,  and  when  the  sympathetic  nervous 
system  is  stimulated  by  certain  depressive  emotional  states  such  as  dis- 
couragement and  anxiety,  brought  on  by  the  disease. 

The  fact  that  the  symptoms  due  to  toxemia  may  be  caused  by  any 
toxic  condition,  whether  it  be  a  tonsillar  focus  or  a  general  intestinal 
toxemia  or  toxins  from  an  acute  infectious  disease,  shows  that  these 
symptoms,  in  themselves,  cannot  be  relied  upon  in  diagnosis  and  are 
only  of  value  when  considered  in  connection  with  other  symptoms  and 
signs.  The  further  fact  that  distinctly  active  conditions  in  tubercu- 
losis are  not  constant  until  the  disease  reaches  a  state  which  is  rather 
widespread  shows  that  this  group  of  symptoms  cannot  be  relied  upon 
for  diagnosis. 

In  order  to  have  a  clear  conception  of  the  symptoms  which  attend 
early  tuberculosis,  we  must  conceive  of  it  as  being  a  chronic  inflamma- 
tory condition  caused  by  irritation  due  to  bacilli  implanted  in  the  tissues 
and  toxins  liberated  by  them.  We  must  further  consider  that  this  chronic 
inflammation  remains  in  a  semi-quiescent  condition  over  prolonged  peri- 
ods of  time  and  that,  in  fact,  these  patients  often  suffer  from  hyper- 
chlorhydria  and  spastic  constipation.  On  the  other  hand,  if  the  sym- 
pathetic tonus  is  greater  these  patients  suffer  from  lack  of  appetite, 
deficiency  of  gastro-intestinal  juices,  a  diminution  of  motility,  a  stasis 
of  the  intestinal  contents  and  rapid  heart  action.  Disturbances  on  the 
part  of  the  heart  follow  the  same  line  as  just  mentioned  in  connection 
with  the  reflex  in  the  gastro-intestinal  tract.  In  those  patients  in  whom 
the  vagus  reflex  predominates  we  may  see,  when  the  patient  is  at  rest 
and  free  from  toxemia  or  general  sympathetic  disturbances,  a  pulse  rate 
normal  or  even  below  normal.  Owing  to  the  fact  that  the  equilibrium 
of  the  pulse  is  disturbed  by  reflex  action  through  both  the  sympathetic 
and  vagus,  the  pulse  is  decidedly  unstable.  AYhile  it  may  be  normal 
or  below  normal,  while  at  rest,  upon  exertion  it  may  become  rapid; 
in  fact,  more  rapid  than  would  occur  under  normal  conditions,  and  the 
normal  is  apt  to  be  restored  more  slowly  than  in  an  individual  who 
does  not  have  this  double  reflex  irritation.  Where  the  sympathetic  tonus 
predominates,  the  pulse  rate  is  higher  than  normal.  Thus,  it  can  be 
seen  that  a  rapid  pulse  must  not  be  expected  under  all  conditions  in 
early  tuberculosis.  Instability  is  the  factor — not  rapidity.  In  observ- 
ing many  tuberculous  patients,  both  in  early  and  chronic  quiescent  or 
semi-quiescent  tuberculosis,  I  have  found  a  pulse  rate  in  the  sixties  to 


94  EAELY  DIAGNOSIS   OF   TUBEECULOSIS 

be  very  common  in  that  type  where  we  would  suspect  a  general 
increased  vagus  tonus  from  other  symptoms. 

Chest  and  shoulder  pains  which  appear  in  tuberculosis  are  of  reflex 
character  and  due  to  two  distinct  causes.  First,  we  have  the  reflex 
sensory  manifestations  which  appear  for  the  most  part  in  the  third  and 
fourth  cervical,  and  the  fourth  dorsal  zones.  Reflex  sensory  pains  in 
tuberculosis  express  themselves,  for  the  most  part,  in  the  scapular  region, 
about  the  third  interspace  anteriorly,  and  in  the  region  of  the  scapulae. 
There  is  also  another  pain  of  reflex  origin  involving  certain  branches 
of  the  cervical  nerves.  This  shows  itself  as  an  aching  of  the  shoulders ; 
and  in  some  instances,  in  advanced  tuberculosis,  I  have  seen  a  deflnite 
inflammation  of  the  brachial'plexus  resulting  from  this  irritation. 

Flushing  of  the  face.  This  is  a  dilation  of  the  capillaries  of  the  head 
and  face  produced  reflexly  through  the  stimulation  of  the  sympathetic 
fibres  which  are  given  off  from  the  second  and  fourth  thoracic  segments 
of  the  cord. 

Apparent  anemia.  It  might  seem  strange  to  speak  of  apparent 
anemia  as  being  a  symptom  of  pulmonary  tuberculosis,  but  it  has  long 
been  observed  that  many  patients  who  suffer  from  early  pulmonary 
tuberculosis  appear  pale  but  do  not  show  the  expected  blood  changes  on 
examination.  The  tuberculous  patient  is  like  the  patient  of  general 
enteroptotic  build.  He  has  a  disturbance  in  the  inspiratory  act,  due, 
however,  to  a  different  cause  from  that  of  the  ptotic  individual.  The 
ptotic  individual  has  a  naturally  deficient  action  of  the  diaphragm,  and 
consequently  a  deficient  inspiratory  act.  The  tuberculous  patient  may 
have  normally  a  full  inspiratory  act,  or  he  may  be  of  the  ptotic  build 
and  have  a  natural  deficiency;  but,  aside  from  his  condition  in  health, 
when  he  has  an  inflammation  in  the  lung,  there  is  a  motor  disturbance 
of  the  muscles  of  inspiration,  including  the  diaphragm,  which  lessens 
the  inspiratory  act. 

The  diaphragm  is  the  chief  muscle  of  respiration.  It  receives  its 
innervation  through  the  phrenics,  which  are  given  off  from  the  third 
and  fourth,  and,  occasionally,  from  the  fourth  and  fifth  cervical  seg- 
ments. These  segments  of  the  cord  are  in  direct  communication,  reflexly, 
through  the  rami  communicant es,  with  the  sympathetics  which  supply 
the  lung.  Consequently  we  have  motor  disturbances  in  the  diaphragm, 
as  well  as  in  the  other  muscles  of  inspiration,  which  result  in  a  deficient 
action  and  limited  motion  of  the  side  of  the  chest  involved.  Inasmuch 
as  the  inspiratory  act  is  one  of  the  chief  factors  in  pumping  the  blood 
from  the  systemic  veins  to  the  right  heart,  we  have  an  interference  with 
this  important  function,  consequently  have  less  blood  delivered  to  the 
right  heart,  and  the  heart  has  less  blood  to  deliver  to  the  arteries.  The 
heart  accustoms  itself  to  a  smaller  content  of  blood  and  becomes 
smaller  than  normal,  as  suggested  by  me  in  a  former  paper  (The  Small 
Heart  in  Tuberculosis:  A  Suggested  Physiological  Explanation.  Jour- 
nal of  the  American  Medical  Association,  April  17,  1915).     Resulting 


F.    M.    POTTENGER,   M.D.  95 

from  these  factors,  we  have  a  disturbance  in  the  general  circulatory 
equilibrium  and  a  relatively  smaller  amount  of  blood  in  the  arteries, 
giving  us  a  relative  arterial  anemia  and  a  relatively  large  amount  of 
blood  stored  up  in  the  systemic  veins,  particularly  the  splanchnics,  giv- 
ing us  venous  congestion. 

In  early  tuberculosis,  the  congestion  does  not  manifest  itself  so  much 
because  the  vessels  are  capable  of  a  considerable  amount  of  compensa- 
tion; but,  in  late  tuberculosis,  this  becomes  quite  evident.  It  will  thus 
be  seen  that  the  symptoms  of  Group  II,  of  the  reflex  origin,  are  much 
like  the  symptoms  of  Group  I,  which  are  due  to  toxemia,  in  that  they 
are  not  distinctive  of  pulmonary  tuberculosis.  They  do  not  point 
directly  to  the  lungs.  Those  in  Group  I  point  to  a  general  sympathetic 
discharge,  involving  a  great  number  of  organs  supplied  by  this  system. 
Those  in  Group  II  point  to  individual  organs  or  parts  which  are  bound 
reflexly  with  branches  of  the  sympathetic  and  vagus  nerves,  and  pro- 
duce symptoms  indicative  of  some  particular  organ  in  which  now  vagus 
tonus  and  again  sympathetic  tonus  predominates. 

The  first  group  of  symptoms  is  only  present  in  this  disease  during 
toxemia  or  during  depressive  emotional  states,  which  are  manifested 
by  fear,  anxiety,  and  discouragement;  while  the  others  may  be  present 
as  long  as  the  inflammation  in  the  lung  is  not  thoroughly  quiescent,  as 
long  as  irritation  of  either  the  sympathetic  or  vagus  nerve  endings  in 
the  lung  exist.  Those  of  Group  I  are  most  prominent  during  attacks 
of  acute  exacerbation  and  are  kept  up  by  wrong  methods  of  living  and 
depressive  emotional  states.  They  are  also  widespread,  involving  a 
great  portion,  if  not  all,  of  the  organs  supplied  by  the  sympathetic 
nervous  system. 

Those  symptoms  of  Group  II,  however,  are  extremely  variable.  The 
reflex  may  express  itself  in  one  organ  for  a  time,  then  in  another  organ, 
and  so  on.  But  some  of  the  sjTuptoms  belonging  to  this  group  are  nearly 
always  present.  That  the  factor  which  is  responsible  for  these  reflex 
symptoms  is  present  over  long  periods  of  time  may  be  inferred  from 
the  persistance  of  such  reflex  signs  as  we  note  in  the  muscles.  In  early 
tuberculosis  the  neck  and  chest  muscles  which  are  involved  in  the  reflex 
show  this  increased  tonus  continuously;  only  now  and  then  do  bacilli 
in  some  particular  focus  take  upon  themselves  increased  activity,  mul- 
tiply, cause  necrosis,  caseation  of  the  tissues  and  produce  the  general 
toxic  symptoms  which  are  recognized  in  diagnosis.  The  disease  process 
is  present  just  the  same,  however,  as  when  the  acute  toxic  symptoms 
are  prominent.  With  this  understanding  of  the  pathology  we  can 
understand  how  unreliable  the  symptoms  in  Group  I  are.  Fortunately 
these  symptoms  are  rarely  found  alone,  and  even  when  they  have  passed 
away,  some  of  the  symptoms  of  the  other  groups,  together  with  certain 
physical  signs,  remain. 

The  particular  characteristic  of  the  symptoms  in  Group  II  is  that 
they  aU  point  to  organs  and  parts  other  than  the  lungs,  but  to  organs 


96  EARLY   DIAGNOSIS   OF   TUBERCULOSIS 

and  parts  which  are  related  to  the  lungs  in  their  nerve  supply.  The 
lungs  are  innervated  by  the  sympathetic  and  vagus  branches  of  the 
autonomic  nervous  system  and  an  irritation  producing  inflammation 
in  one  branch  of  these  systems  is  apt  to  express  itself  in  reflex  action  in 
other  branches  of  the  same  system.  Consequently,  inflammation  in  the 
lungs  sends  impulses  centrally,  which  manifest  themselves  in  reflex 
action  in  other  organs  and  parts  connected  centrally  with  the  fibres 
which  supply  the  lung.  In  this  way  all  symptoms  found  in  Group  II 
may  be  explained.  For  example,  hoarseness,  tickling  in  the  larynx 
and  cough  are  reflex  through  the  pulmonary  branches  of  the  vagus  and 
superior  and  inferior  laryngeal  nerves.  The  hoarseness  may  be  due  to 
reflex  irritation  of  either  the  superior  or  inferior  laryngeal  nerve.  When 
due  to  the  superior  laryngeal  nerve,  the  picture  in  the  larynx  is  that  of 
a  relaxed  cord.  The  superior  laryngeal  nerve  furnishes  sensation  to  the 
larynx  and  motor  power  to  the  crico-thyroid  muscle,  the  contraction  of 
which  increases  the  tension  of  the  cord.  When  this  is  irritated  reflexly, 
we  note  a  general  relaxation  and  interference  with  normal  approxima- 
tion, particularly  of  the  central  portions  of  the  cords.  When  hoarseness 
is  due  to  interference  with  the  recurrent  laryngeal,  it  shows  itself  often 
as  an  adductor  paralysis,  the  cord  of  the  affected  side  failing  to  approxi- 
mate its  fellow  on  the  other  side.  Tickling  in  the  larynx  is  a  sensory 
reflex  through  the  superior  laryngeal.  The  tickling  in  the  larynx  is  the 
sensory  impulse  which  precedes  cough.  Indigestion  and  loss  of  weight 
and  reflex  symptoms  on  the  part  of  the  gastro-intestinal  tract  are  varied. 
They  depend  considerably  upon  the  individual.  There  are  individuals,  as 
shown  by  Eppinger  and  Hesz  (Die  Vagotonic.  Sammlung.  Klinischer 
Abhandlungen.  von  Noorden.  Heft  9  u.  10,  1910),  who  naturally  have 
increased  vagus  tonus.  There  are  others  in  whom  the  sympathetic  tonus 
seems  to  predominate.  The  nature  of  the  reflex  symptoms  on  the  part  of 
the  digestive  tract  in  tuberculosis  will  depend  considerably  on  the  indi- 
vidual's relative  vagus  and  sympathetic  tonus.  Here  we  have  the  inflam- 
mation in  the  lung  sending  impulses  reflexly  to  the  gastro-intestinal 
tract  through  both  the  vagus  and  the  sympathetic.  If  the  vagus  tonus 
predominates,  and  it  seems  to  do  so  in  early  tuberculosis  for  the  most 
part,  when  the  patient  is  not  toxic,  he  may  have  even  a  better  appetite 
than  normal.  There  also  may  be  an  ample  supply  of  gastric  and  intes- 
tinal juices  and  the  motility  of  the  gastro-intestinal  tract  may  be  above 
normal  until  healing  occurs.  We  must  assume  that  the  reflex  impulses 
which  produce  manifestations  on  the  part  of  other  organs  are  also  con- 
tinuous, but  that  at  times  the  equilibrium  is  maintained  and  dysfunc- 
tion does  not  appear. 

If  we  take  up  the  symptoms  in  Group  III  it  will  be  noticed  at  once 
that  these  differ  from  Group  I  and  II  in  one  important  particular.  With 
the  exception  of  temperature,  they  all  point  to  the  lung.  When  we  have 
sufficient  inflammation  in  the  lung  to  produce  a  tuberculous  bronchi- 
tis, it  manifests  itself,  as  a  rule,  in  a  cough  which  is  not  unlike  acute 


F.    M.    POTTENGER,    M.D.  97 

bronchitis  and  hangs  on  for  an  uncertain  time.  In  cold  weather  a 
bronchitis  that  hangs  on  for  several  weeks,  or  any  bronchitis  which  is 
repeated  at  intervals,  should  be  considered  as  suspicious.  A  bron- 
chitis of  this  kind  nearly  always  has  associated  with  it  the  symptoms  in 
Group  I  and  some  of  the  symptoms  in  Group  II.  This  should  be  suf- 
ficient, if  properly  correlated,  to  make  the  diagnosis  of  pulmonary  tuber- 
culosis extremely  probable.  These  attacks  of  tuberculous  bronchitis  may 
not  come  often.  They  are  like  the  exacerbations  which  produce  toxic 
symptoms  in  this  particular.  They  may  be  months  apart  and  sometimes 
years.  Sometimes  they  show  only  as  winter  coughs  which  continue 
winter  after  winter  until  a  definite  advanced  tuberculosis  manifests 
itself. 

Spitting  of  blood  may  come  suddenly  without  any  other  symptoms 
being  present.  This  occurs  when  bleeding  is  due  to  the  rupture  of  a 
small  vessel,  caused  by  an  old  quiescent  focus  of  small  dimensions. 
Under  such  conditions,  however,  if  there  is  an  extension  of  the  disease 
following  the  spitting  of  blood,  it  will  probably  be  followed  by  some 
of  the  symptoms  in  Group  II ;  and  others  in  Group  I  will  appear.  The 
same  may  be  said  if  symptoms  of  activity  accompany  the  hemorrhage. 
The  spitting  of  blood  should  always  be  considered  as  tuberculous,  unless 
some  other  cause  can  be  definitely  proven. 

Pleurisy  has  a  definite  meaning.  In  a  very  large  percentage  of  cases 
it  is  tuberculous.  It  further  is  evidence  of  an  active  tuberculosis.  The 
profession  must  learn  that  tuberculosis  of  the  pleura  is  as  serious  as 
tuberculosis  of  any  other  organ,  with  the  exception  that  it  is  usually 
limited  in  extent  and,  if  properly  regarded,  offers  the  patient  a  chance 
for  cure.  Tuberculous  pleurisy  is  a  metastasis  from  some  other  focus  in 
the  body  which  must  be  active  or  the  metastasis  could  not  occur.  Conse- 
quently it  should  he  treated  seriously.  If  the  fact  that  there  is  an 
involvement  in  the  pleura  is  not  of  sufficient  consequence  in  the  mind  of 
the  practitioner,  that  other  fact — that  this  is  an  extension  from  some 
other  focus  which  is  active  or  the  extension  could  not  occur — should  be 
of  sufficient  consequence  to  cause  this  symptom  to  be  treated  seriously. 
This  symptom  itself  should  make  a  diagnosis,  unless  it  can  be  definitely 
proven  that  the  pleurisy  is  due  to  some  other  cause.  This  applies  to 
dry  pleurisy,  the  same  as  to  pleurisy  with  effusion.  Symptoms  of  the 
other  groups  may  not  be  present  if  the  pleurisy  is  only  of  mild  degree 
and  limited  in  its  extent.  As  a  rule,  however,  symptoms  in  Group  I 
will  manifest  themselves  during  this  time  and  some  of  those  in  Group  II. 

While  sputum  is  not  an  early  sign  in  tuberculosis,  yet  it  is  often 
present  much  earlier  than  we  anticipate.  Whenever  the  pathological 
process  in  the  lung  is  sufficiently  extensive  and  sufficiently  virulent  to 
cause  an  exudation  in  the  tissues,  there  may  be  a  slight  amount  of 
sputum  present.  At  first  this  may  be  only  mucus,  but  sooner  or  later 
necrosis  and  caseation  of  small  tubercles  occur  and  bacilli  may  be  found. 
Sputum  should  always  be  examined  regardless  of  the  patient's  opinion 


98  EARLY  DIAGNOSIS  OF  TUBERCULOSIS 

as  to  its  nature.  It  is  not  sufficient  for  the  patient  to  say  that  he  has  no 
expectoration.  Give  the  patient  suffering  from  early  tuberculosis  a  bottle 
and  require  him  to  bring  for  examination  all  the  sputum  raised  in 
twenty-four  hours,  forty-eight  hours  or  even  seventy-two  hours.  This 
sputum  should  be  treated  not  only  according  to  the  ordinary  methods 
of  examination,  but  either  by  antiformin  or  by  fermentation  and  shaking. 
If  this  careful  procedure  is  followed,  one  will  be  surprised  by  often 
finding  bacilli  where  unsuspected.  The  danger  of  basing  a  diagnosis 
upon  the  examination  of  a  single  sample  of  sputum  in  a  patient  with 
early  tuberculosis  can  be  understood  if  we  realize  that  while  the  patient 
may  expectorate  six  or  eight  times  a  day,  he  might  not  expectorate 
bacilli  more  than  once  in  the  entire  twenty-four  hours,  or  once  in  two 
or  three  days.  The  examination  of  a  sample,  unless  bacilli  are  found, 
is  worthless. 

Where  bacilli  are  not  found,  the  lymphocyte  content  should  be  noted. 
In  tuberculous  sputum  there  is  often  a  high  lymphocyte  count.  If  40  or 
50  per  cent,  of  lymphocytes  should  be  found,  it  should  be  considered  as 
suspicious.  When  lymphocytic  or  bacillary  sputum  is  found,  some  of 
the  other  symptoms  are  nearly  always  present. 

A  continued  temperature  was  formerly  thought  to  be  tuberculous. 
This  is  not  necessarily  true.  Any  toxemia  will  produce  temperature. 
Any  inflammation  will  produce  temperature,  and  now  that  we  know  that 
infectious  foci  may  be  found  in  other  parts  of  the  body,  we  must  be  very 
guarded  in  interpreting  a  slight  rise  of  temperature  as  being  due  to 
tuberculosis. 

Temperature  must  have  other  signs  and  symptoms  accompanying  it. 
Temperature  in  tuberculosis  is  extremely  variable.  It  depends  a  great 
deal  on  whether  the  patient  is  at  rest  or  active.  The  inflammation  in 
tuberculosis  is  not  constant  but  goes  in  waves.  There  are  waves  of 
activity  when  the  temperature  will  be  a  little  higher  than  normal  and 
waves  of  quiescence  when  it  will  be  normal.  No  temperature  curve  in 
suspected  tuberculosis  is  of  any  diagnostic  value  unless  it  extends  over 
a  period  of  several  weeks.  The  temperature  accompanying  the  menstrual 
period  in  women  must  be  understood.  For  some  time,  anywhere  from 
a  few  days  to  two  weeks  prior  to  the  period  time,  the  temperature  is,  as 
a  rule,  higher  than  the  two  weeks  following  the  onset  of  the  menses. 
It  is  not  uncommon  to  find  a  temperature  running  from  98  degrees  to 
98.6  degrees  for  the  two  weeks  following  the  period  and  running  from 
98.4  degrees  to  99  degrees  during  the  two  weeks  preceding  the  period. 
This,  however,  shows  great  variation.  Premenstrual  rises  may  only 
appear  a  day  or  two  before  the  onset  of  the  period.  In  some  women  it 
is  even  slightly  lower,  but  the  period  is  followed  by  several  days'  rise. 

We  can  see  from  the  above  discussion  of  the  symptoms  in  tuberculosis 
that  if  they  are  properly  analyzed,  they  give  us  diagnostic  evidence;  if 
not,  they  are  confusing.  By  bearing  in  mind  that  they  are  produced  by 
three  different  forces — toxemia,  reflex  action  and  the  tuberculous  process 


F.    M.   POTTENGEE,  M.D.  99 

itself — we  can  understand  them  better  and  analyze  them  to  greater 
advantage  than  we  have  been  able  to  do  with  our  hitherto  indefinite 
ideas  of  their  causation. 

Now  if  we  take  up  the  question  of  the  physical  signs,  we  shall  see 
how  intimately  they  are  associated  with  the  symptoms.  For  example, 
we  often  see  a  dilatation  of  the  pupils  on  the  side  of  the  involvement. 
This  dilatation  of  the  pupil  is  inconstant.  Some  observers  have  reported 
that  they  have  found  it  in  about  50  per  cent  of  cases.  It  must  be  remem- 
bered that  this  was  probably  on  a  single  examination  of  each  patient, 
not  a  continuous  observation.  The  pupil  is  innervated  by  both  the  vagus 
and  sympathetic  fibres;  the  vagus  has  a  tendency  to  contract — the  sym- 
pathetic to  dilate ;  consequently  the  equilibrium  is  disturbed.  At  times 
the  patient  may  have  a  contracted  pupil ;  again,  he  may  have  a  normal 
pupil,  and,  still  again,  a  dilated  pupil.  Dilatation  of  the  pupil  is 
extremely  common  if  we  observe  patients  repeatedly  during  various 
portions  of  the  day  over  long  periods  of  time.  When  we  find  dilatation 
of  the  pupil  on  one  side,  or  abnormal  dilatation  on  both  sides,  we  think 
at  once  of  reflex  disturbances  from  the  lung. 

Other  very  important  physical  signs  which  I  have  described  are  those 
of  motor  and  tropic  disturbances  in  the  muscles,  subcutaneous  tissue 
and  skin  over  the  chest.  These  disturbances  in  the  skeletal  muscles,  sub- 
cutaneous tissue  and  skin  overlying  them,  are  due  to  reflex  action. 

The  inflammation  in  the  lung  sends  afferent  impulses  through  the 
sympathetic  and  the  rami  communicant es  to  the  cervical  segments  of 
the  cord,  where  they  transfer  their  irritation  to  the  cell  bodies  which 
give  origin  to  filaments  of  the  cervical  nerves.  This  being  the  portion 
of  the  cord  which  provides  motor,  sensory,  and  trophic  impulses  for  the 
superficial  muscles  of  the  chest  and  the  skin  and  subcutaneous  tissue 
overlying  them,  also  motor  and  trophic  impulses  for  the  diaphragm,  we 
find  an  expression  of  the  refiex  in  functional  and  structural  changes  in 
these  structures. 

In  the  case  of  the  sterno-cleido-mastoideus  and  trapezius  muscles 
we  also  have  another  reflex  through  the  filaments  of  the  accessorius 
running  in  the  vagus.  The  refiexes  manifested  by  these  structures  give 
us  extremely  important  signs  by  which  we  may  interpret  the  pathology 
within  the  chest.  During  periods  of  active  infiammation  in  the  lung  and 
as  long  as  the  involvement  in  the  lung  has  not  healed,  nerve  endings  are 
irritated,  impulses  travel  centrally  and  continue  their  reflex  irritation 
of  nerve  fibres  which  supply  these  superficial  tissues.  Consequently, 
we  have,  in  the  presence  of  early  active  inflammation  in  the  lung,  a 
motor  reflex  manifesting  itself  in  the  superflcial  muscles  as  an  increased 
tone  (spasm).  In  the  diaphragm  it  shows  as  altered  motion.  This  in- 
creased tone  in  the  superficial  muscles  may  be  determined  sometimes  on 
sight,  but  particularly  on  palpation.  The  muscles  are  firmer  than  nor- 
mal; the  individual  fibres  seem  to  have  a  definitely  increased  tone.  It 
is  shown  in  the  diaphragm  as  limited  motion  of  the  side.    Another  ele- 


100  EARLY  DLIGNOSIS  OF  TUBERCULOSIS 

ment,  of  course,  comes  in  to  produce  this  sign — decreased  elasticity  of 
the  pulmonary  tissue  itself.  That  this  limited  motion  of  the  side  can 
be  caused  by  reflex  disturbance  on  the  part  of  the  muscles  of  inspiration 
can  be  proven  by  the  fact  that  a  very  small  lesion  in  the  apex, 
where  there  is  not  sufficient  disturbance  on  the  part  of  the  pulmonary 
elasticity  to  produce  any  appreciable  effect,  will  produce  limited  motion. 

When  the  disease  has  persisted  for  a  long  period  of  time,  as  it  does 
in  advanced  tuberculosis,  we  have  a  reflex  trophic  disturbance  in  all 
the  parts  innervated — the  muscles,  subcutaneous  tissue  and  skin.  The 
muscles  also  suffer  a  degeneration  from  the  fact  that  they  are  kept  in 
constant  tonus  for  a  prolonged  period  (overwork  atrophy) .  Consequently 
when  we  find  a  distinct  degeneration  of  the  muscles,  subcutaneous  tissue 
and  the  skin  limited  to  the  tissues  covering  one  apex  or  both  apices, 
we  should  at  once  think  of  reflex  action  as  being  the  etiological  factor. 
When  an  inflammation  has  existed  in  the  lung  for  a  prolonged  period  of 
time,  as  tuberculous  infiltrations  do,  the  skin  is  usually  thinner  than 
normal,  the  subcutaneous  tissue  is  wasted,  and  when  picked  up  between 
thumb  and  finger,  shows  a  diminution  and  distinct  atrophy  as  com- 
pared with  that  over  the  other  apex  or  over  other  parts  of  the  chest 
wall.  The  muscles  take  upon  themselves  certain  definite  changes.  They 
lose  their  elasticity  and  appear  to  the  palpating  finger  more  or  less 
doughy.  The  bundles  also  are  more  easily  detected  than  in  normal 
muscle  and  give  the  impression  of  being  stringy. 

The  importance  of  this  localized  atrophy,  as  indicating  chronic  inflam- 
mation in  the  lung,  cannot  be  overestimated.  If  activity  is  also  present 
then,  aside  from  the  atrophy,  a  tendency  for  the  muscles  to  show 
increased  tonus  may  also  be  detected  when  carefully  examined ;  although 
the  general  muscle  tone  is  so  low  from  the  degeneration  that  this  may 
be  difficult  to  detect. 

The  diaphragm  reflex  may  be  detected  as  a  limited  motion  of  the  side, 
by  either  inspection  or  palpatation.  We  sometimes  find  difficulty  in  dis- 
tinguishing between  the  motor  and  trophic  disturbance  in  the  muscles, 
which  are  produced  by  reflex  irritation  and  that  which  is  produced  by 
occupation.  AVe  have  certain  definite  criteria,  however,  which  will  aid 
us  if  we  find  increased  tone  of  the  muscles  confined  to  one  side,  partic- 
ularly the  right  side,  in  men  who  do  heavy  work.  If  this  is  due  to  occu- 
pation it  is  not  so  apt  to  involve  the  sterno-cleido-mastoideus  as  other 
muscles  and  will  not  involve  the  diaphragm.  Consequently,  if  we  find 
increased  tonus  of  the  muscles,  which  would  show  this  change  of  occu- 
pation, and  also  find  the  diaphragm  reflex — lagging  on  the  side — and 
increased  tonus  in  the  sterno-cleido-mastoideus,  we  should  suspect  it  to 
be  due  to  reflex  action  produced  by  inflammation  in  the  lung.  It  will 
also  be  noted  that  there  is  some  atrophy  of  the  muscles  on  the  right  side 
of  most  chests,  due  to  occupational  influences.  Sometimes  it  is  extremely 
confusing  to  tell  whether  this  is  wholly  occupational  or  whether  part  of 
it  is  reflex  as  well.     There  are  certain  signs,  however,  which  also  aid  in 


F.    M.    POTTENGER,    M.D.  101 

this  dilemma.  I  would  call  attention  to  the  fact  that  the  sterno-cleido- 
mastoideus  rarely  degenerates  from  overwork.  Nor  does  the  subcutan- 
eous tissue.  Consequently,  if  we  find  a  degeneration  of  the  stemo-cleido- 
mastoideus  along  with  the  other  muscles  and  also  find  the  subcutaneous 
tissue  overlying  the  muscles  atrophied,  then  we  are  justified  in  suspect- 
ing a  degeneration  due  to  pathological  changes  within  the  lung. 

It  is  important  to  note  that  these  reflexes  are  bound  up  and  closely 
associated  with  the  reflex  symptoms  found  in  Group  II.  They  are  also 
accentuated  at  times  when  those  symptoms  in  Group  I  are  most  prom- 
inent. 

Physical  signs  which  have  long  been  employed  in  the  diagnosis  of 
intrapulmonary  conditions  are  the  lagging  of  the  chest  wall  and  the 
changes  on  percussion  and  auscultation.  Lagging  of  the  chest  wall,  as 
previously  mentioned,  is  due  to  both  reflex  motor  disturbances  in  the 
muscles  of  inspiration  and  lessened  elasticity  in  the  pulmonary  tissue. 
To  be  sure,  it  is  also  produced  by  acute  pleurisy  and  pleural  adhesions, 
but  this,  as  a  rule,  does  not  have  so  much  to  do  with  early  tuberculosis. 

The  changes  on  percussion  and  auscultation  are  usually  considered  to 
be  due  wholly  to  a  tuberculous  process  in  the  lung,  but  this  is  untrue. 
Some  of  our  greatest  errors  and  some  of  the  things  which  have  disturbed 
us  most  in  diagnosis  have  been  due  to  this  assumption.  A  moment's 
thought  will  prove  that  we  cannot  neglect  the  influence  of  the  superficial 
tissues  on  percussion  and  auscultation.  When  we  see,  as  I  have  pre- 
viously described,  how  these  are  altered  in  the  presence  of  activity  and 
chronic  inflammation  in  the  lung,  it  can  readily  be  seen  that  this 
influence  must  be  taken  into  consideration  in  interpreting  our  signs  on 
percussion  and  auscultation.  The  resistance  to  the  finger  or  the  char- 
acter of  the  sound  emitted  by  the  percussion  blow  is  made  up  not  only 
by  the  involvement  in  the  lung,  but  the  involvement  in  the  lung,  plus 
the  soft  parts,  bony  thorax  and  all  other  conditions  present  in  the  chest. 
Consequently,  if,  through  a  chronic  inflammation  we  have  a  degenera- 
tion which  amounts  to  a  wasting  of  any  considerable  portion  of  the  soft 
tissue,  this  must  be  taken  into  consideration  in  our  percussion  findings. 
It  is  not  at  all  uncommon  to  find  one-third  of  the  soft  tissue  covering 
an  apex  wasted,  through  the  reflex  trophic  disturbances  caused  by  the 
chronic  inflammation  in  the  underlying  lung.  It  would  be  necessary  to 
have  a  very  dense  infiltration  in  that  apex  in  order  to  make  the  per- 
cussion note  equal  in  pitch  to  that  on  the  normal  side ;  or  make  the  finger 
resistance  equal  to  that  on  the  normal  side.  The  percussion  note  and 
resistance  to  the  finger  also  depend  on  the  tone  of  the  muscle.  If,  as 
in  early  tuberculosis,  we  have  an  increased  tonicity  of  the  muscle,  this, 
of  itself,  gives  a  higher  pitched  note  and  increased  resistance  as  compared 
with  the  normal  muscle ;  and  a  normal  muscle  will  give  higher  pitch  and 
increased  resistance  to  the  finger  as  compared  with  the  degenerated 
muscle.  I  doubt  not  that  every  man  who  examines  chests  has  been 
annoyed  and  perplexed  very  often  because  of  his  failure  to  recognize 


102  EARLY  DIAGNOSIS  OF  TUBERCULOSIS 

the  effect  of  the  soft  tissue.  It  is  impossible  to  compare  the  percussion 
findings  in  two  parts  of  the  chest  or  over  symmetrical  portions  of  the 
two  lungs  without  first  taking  into  consideration  the  relative  thickness 
and  relative  tonicity  of  the  muscles  and  soft  tissues  over  the  different 
parts.    This  is  extremely  important  in  early  tuberculosis. 

One  can  readily  understand  how  the  auscultation  findings  are  also 
influenced  by  the  condition  of  the  muscles.  If  one  will  listen  over  a 
degenerated  muscle  or  a  relaxed  muscle,  and  then  over  the  same  muscle 
when  in  a  state  of  tonicity,  he  will  see  that  an  impediment  has  been 
placed  in  the  way  of  the  conduction  of  sound  through  the  muscles  when 
in  increased  tone.  He  will  also  see  that  the  sounds  are  higher  pitched 
over  muscles  with  increased  tone  when  compared  with  the  normal. 

To  sum  up,  we  can  now  understand  that  all  the  symptoms  of  tuber- 
culosis are  an  expression  of:  toxemia,  reflex  action,  or  of  the  disease 
process  itself.  The  physical  signs  which  accompany  tuberculosis  are  also 
due  to  reflex  action,  and  the  tuberculous  process  itself.  We  can  also 
see  that  the  interpretation  of  the  data  obtained  by  the  usual  methods 
of  examination,  inspection,  palpation,  percussion  and  auscultation,  can- 
not be  correct  unless  we  take  into  consideration  not  only  the  pathological 
process  within  the  lung,  but  also  the  changes  which  occur  in  all  soft 
tissues  covering  the  thorax.  To  be  more  exact,  we  must  take  into  con- 
sideration the  soft  structures,  the  bony  thorax,  the  infiltration  in  the  lung 
and  all  other  conditions  which  surround  it. 

In  conclusion,  I  trust  that  this  analysis  of  the  clinical  symptoms  and 
physical  signs  of  tuberculosis  may  prove  as  valuable  to  you  in  your 
work  as  it  has  been  to  me  in  mine,  and  I  further  trust  that  it  may  give 
you  a  clearer  insight  into  this  complex  disease,  and  thus  aid  in  the 
making  of  early  diagnosis. 


COMPLEMENT  FIXATION  IN  TUBERCULOSIS 
By  H.  J.  CoRPEE,  M.D. 

CHICAGO 

The  discovery  of  the  tubercle  bacillus  by  Koch  in  1882  placed  the 
diagnosis  of  tuberculosis  on  a  substantial  foundation,  but  the  bacillus 
cannot  always  be  demonstrated  early  in  the  discharges,  and  frequently 
never  appears.  It  also  gives  little  clue,  even  if  present,  to  the  activ- 
ity or  inactivity  of  the  disease.  Clinical  findings  fail  to  give  us 
any  direct  information  regarding  activity  or  inactivity  except  in  a 
crude  way.  Thus  far  biological  methods  of  diagnosis  have  been  of  little 
practical  value  with  one  exception — complement  fixation,  which,  though 
not  fulfilling  the  early  expectations,  is  gradually  being  improved  so  that 
there  is  still  promise  of  a  method  being  developed  of  equal  diagnostic 
value  to  the  Wassermann  reaction  in  syphilis. 

The  discoveries  that  led  to  the  complement  fixation  test  date  back 
to  1874,  when  Traube,^  making  observations  on  blood,  concluded  that 
blood  is  able  to  destroy  bacteria.  Lister,  in  1881,  noted  that  extravascular 
blood  remains  sweet  despite  the  addition  of  small  amounts  of  putrefying 
material.  NuttalP  in  1888  observed  that  the  destruction  of  organisms 
occurred  in  the  aqueous  humour  and  pericardial  fluid  free  from  cells. 
He  also  noted  that  56  degrees  Centigrade  destroyed  this  bactericidal 
activity,  which  became  of  practical  applicability  in  destroying  one  of  the 
constituents  required  in  the  complement  fixation  reaction. 

A  decided  advance  was  made  when  Pfeiffer  observed  that  the  cholera 
vibrio  contains  endotoxins  in  contradistinction  to  the  diffusible  toxins 
of  the  diphtheria  bacillus  and  that  immunity  against  these  bacteria  is 
produced  by  means  other  than  simple  neutralization  of  diffusible  toxin. 
These  observations  led  to  the  demonstration  by  Pfeiffer  and  Bordet  of 
the  complex  nature  of  the  bactericidal  process;  in  short,  to  the  demon- 
stration of  complement  in  normal  sera  and  the  development  of  immune 
bodies  or  amboceptors  in  the  immunized  animal. 

Pfeiffer 's  reaction  may  be  observed  in  one  of  two  ways:  either  (1) 
by  rendering  a  guinea  pig  highly  immune  by  successive  inoculation  of 
virulent  cholera  vibrio  and  then  introducing  into  its  peritoneal  cavity 
five  to  ten  times  the  ordinary  fatal  dose  of  an  agar  culture  of  cholera 
vibrio,  or  (2)  injecting  into  a  normal  guinea  pig  a  like  dose  of  cholera 
vibrio  with  an  excess  of  cholera  immune  serum  from  another  guinea  pig. 
In  either  case  by  removing  with  a  pipette  some  of  the  peritoneal  fluid 
from  time  to  time,  it  is  seen  that  the  injected  bacteria  undergo  destruc- 
tion and  this  apart  from  any  phagocytosis.  As  Pfeiffer  says:  "They 
undergo  solution  like  sugar  does  in  water."  Later  Metchnikoff  and 
Bordet  showed  that  the  same  thing  occurred  in  vitro  by  using  definite 

1.  Adami.     Principles  of  Pathology,  Vol.  I,  1910,  p.  542. 

2.  ZeitBcfar.  f.  Hygiene,  4,  1888,  p.  253. 

108 


104  COMPLEMENT   FIXATION    IN   TUBERCULOSIS 

proportions  of  bacilli,  inactivated  (heated)  immune  serum,  and  normal 
serum.  Loefifler  and  Abel  (1896)^  showed  that  the  amboceptors  thus 
developed  were  far  more  specific  than  agglutinins  and  are  unaffected 
by  heating  several  hours  at  60  degrees  Centigrade,  but  are  destroyed  at 
70  degrees  Centigrade.  They  are  not  immediately  produced  upon  inocu- 
lating animals  with  bacteria,  but  usually  require  a  lapse  of  three  to  four 
days.  Once  developed  they  can  be  recognized  for  a  considerable  period 
of  time. 

(demonstration  OF  hemolysis) 

To  Bordet  and  Gengou,  who  in  1901  reported  their  results,  we  owe 
the  discovery  of  the  Bordet-Gengou  phenomenon  of  complement  fixation. 
To  Bordet  we  owe  the  observation  that  if  sensitized  red  corpuscles 
(i.  e.,  corpuscles  which,  placed  in  immune  serum,  have  taken  up  ambo- 
ceptor) be  placed  in  normal  unheated  serum  they  take  up  all  the  com- 
plement, so  that  now  this  serum  becomes  wholly  inactive  for  bacteriolytic 
or  other  cytolytic  purposes.  Similarly,  if  bacteria  be  sensitized,  they 
absorb  or  fix  all  the  complement  in  normal  serum  subsequently  added. 
Gengou  showed  that  a  like  fixation  of  complement  takes  place  under 
conditions  in  which  complement  plays  no  part  in  the  main  process. 
Thus,  if  to  an  immune  precipitin  serum  a  trace  of  the  antigen  (protein) 
be  added,  even  though  the  precipitate  be  so  minute  as  to  be  invisible,  the 
complemental  bodies  present  in  the  serum  become  fixed  and  the  serum 
subsequently  cannot  be  employed  to  activate  sensitized  erythrocytes,  etc. 
The  same  is  true  when  toxin  and  antitoxin  unite,  a  resultant  fixation  of 
complement  occurs. 

The  first  practical  successful  application  of  the  Bordet-Gengou  phe- 
nomenon was  developed  by  Wassermann  and  Briick  in  1906,  when  they 
discovered  the  Wassermann  reaction  for  syphilis.  Even  before  this,  work 
had  been  done  on  complement  fixation  for  tuberculosis  but  with  very 
discouraging  results.  The  materials  and  methods  used  to  date  have, 
however,  been  open  to  severe  criticism,  and  with  slight  advances  and 
improvements  the  percentage  efficiency  of  the  method  may  be  gradually 
increased  and  the  future  may  still  reveal  a  method  of  high  practical 
applicability  which  may  approach  or  even  exceed  the  Wassermann 
reaction  in  diagnostic  value. 

The  first  application  of  complement  fixation  in  tuberculosis  was  made 
by  Widal  and  LeSourd  in  1901,^  who  published  the  first  results  with  the 
method  as  applied  to  tuberculosis.  They  obtained  deviation  of  comple- 
ment in  certain  cases  of  tuberculosis,  using  as  antigen  homogeneous  emul- 
sions of  tubercle  bacilli  of  the  Arloing-Courmont  strain.  This  was  fol- 
lowed by  a  demonstration  in  1903  by  Bordet  and  Bengou^  of  the  presence 
of  antibody  capable  of  uniting  with  tubercle  bacilli  and  fixing  complement 

3.  Centralbl.  f.  Bakt.,   19,  1896,  p.  51. 

4.  Taken  from  article  by  Theodore  Shennan  and  James  Miller.  Edinburgh  Medical  Jour., 
Vol.  X,  1913,  pp.  81-85. 

5.  J.  Bordet  and  O.  Gengou.     Compt.  rend.  Acad,  de  Sci.,  1903,  CXXXVII.,  p.  351. 


H.    J.    CORPEK,    M.D.  •  105 

in  the  sera  of  tuberculous  animals.  "Wassermann  and  Briick^  in  1906 
demonstrated  the  presence  of  an  antibody  toward  tuberculin  in  patients 
treated  with  tuberculin,  but  only  examined  13  cases  of  pulmonary  tuber- 
culosis. Caulfield^  (1911)  examined  104  cases  of  pulmonary  tuberculosis 
with  bacillary  emulsion  as  antigen  and  obtained  33  per  cent  Turban  I 
cases,  70  per  cent  Turban  II,  and  62  per  cent  Turban  III  positive  results. 
Laird  (1912)^  examined  34  cases,  making  84  tests,  and  obtained  24  posi- 
tives (in  4  cases),  using  watery  emulsion  of  tubercle  bacilli  (which  he 
does  not  describe),  but  his  results  were  inconclusive.  Hammer,^  using 
O.T.  and  extracted  tuberculous  nodules,  obtained  97  per  cent  positive 
results  in  46  tuberculous  cases.  Calmette  and  Massol,^*^  using  prepara- 
tions made  from  tubercle  bacilli  by  extracting  with  water  and  peptone, 
obtained  in  134  cases  92.5  per  cent  fixation  altogether. 

Fraser  (1913),^^  testing  a  large  variety  of  antigens,  found  that  living 
tubercle  bacilli  gave  no  fixation  in  96.6  per  cent  of  normal  individuals, 
while  42.3  per  cent  of  tuberculous  individuals  gave  positive  reactions. 
Syphilitics  also  gave  a  fairly  high  percentage  of  positive  results.  She 
states  that  the  most  reliable  antigen  is  prepared  from  human  living 
bacilli,  and  that  diagnostically  the  complement  fixation  test  with  living 
bacilli  is  of  more  value  from  the  standpoint  of  positive  results  than  any 
other  reaction  discovered  to  date.  She  believes  the  absence  of  antibodies 
accounts  for  the  low  percentage  of  results  obtained.  Dudgeon,  Meek  and 
"Weir^^  also  tested  a  large  number  of  antigens  and  in  102  untreated  cases 
obtained  86  positive,  while  all  cases  treated  with  tuberculin  gave  positive 
results.  Products  of  the  bacilli  themselves  were  found  to  be  most  satis- 
factory as  antigen.  With  an  alcoholic  antigen^^  ^*  prepared  from  tubercle 
bacilli  they  obtained  of  a  total  of  234  cases,  209  (89.3  per  cent)  positive, 
194  of  these  on  first  examination,  11  (of  the  15  negative)  on  second 
examination,  and  4  more  on  the  third  examination.  Besredka^^  (1913) 
prepared  an  antigen  by  growing  tubercle  bacilli  (of  a  questionable  nature 
since  they  grow  in  24  to  48  hours)  on  egg  bouillon,  heating  and  filtering. 
With  this  antigen  Bronfenbrenner^*'  (1914)  obtained  a  very  high  per- 
centage of  positive  results,  93.8  per  cent  in  active  cases  and  55.5  per  cent 
in  convalescents,  while  suspected  cases  gave  75  per  cent  and  syphilitic 
sera  24  per  cent  positive  reactions.  Inman^^  and  Kuss,  Leredde  and 
Rubenstein^^  found  this  antigen  not  to  be  specific.  Mcintosh,  Fildes  and 
Radcliffe^®  (1914)  also  justly  criticized  Besredka's  antigen  and  conclude, 

6.  A.  Wassermann  and  C.  Briick.     Deut.  Med.  Wochschr.,  1906,  XXXII,  p.  449. 

7.  H.  Caulfield.     J.  Med.  Research,  24,  1911,  p.  122. 

8.  A.  T.  Laird.     J.  Med.  Research,  27,  N.  S.  22,   1912,  p.  163. 

9.  C.  Hammer.     Miinch.  med.  Wochschr.,  1912,  LIX,  p.  1750. 

10.  Calmette  and  Massol.     Compt.  rend.  Soc.  de  Biol.,  1912,  LXXIII,  pp.  120  and  122. 

11.  Elizabeth  Frazer.     Zeitschr.  f.  Immunitats.       Orig.  20,  1913,  pp.  291-299. 

12.  Leonard  S.  Dudgeon,  W.  0.  Meek  and  H.  B.  Weir.     Lancet,  1913,  Vol.  184,  pp.  19-21. 

13.  Leonard  S.  Dudgeon.     Jour.  Hygiene,  1914,  Vol.  14,  pp.  52-71. 

14.  Dudgeon,  Meek  and  Weir.     Ibid.     Pp.  72-75. 

15.  A.  Besredka.     Compt.  rend.  Acad,  de  Sci.,   1913,  CLVI,  p.   1633. 

16.  J.  Bronfen-Brenner.     Arch.  Int.  Med.,   1914,  XIV.,  pp.  786-803. 

17.  A.  C.  Inman.     Compt.  rend.  Soc.  de  Biol.,  1914,  76,  p.  251. 

18.  Kuss,  Leredde  and  Rubenstein.     Ibid.     1914,  76,  p.  244. 

19.  J.  Mcintosh,  A.  Fildes  and  J.  A.  D.  Radclifife.     Lancet,   1914,  p.  485. 


106  COMPLEMENT   FIXATION   IN   TUBERCULOSIS 

after  testing  a  large  number  of  antigens,  tliat  the  living  bacillary  emul- 
sion is  best,  giving  76.7  per  cent  positive  results  in  43  definite  eases  of 
phthisis,  80.7  per  cent  in  surgical  tuberculosis,  37.5  per  cent  in  glandular, 
and  87  normal  individuals  only  gave  3  positive  reactions  (2  of  these 
were  in  lepers  and  one  in  a  case  of  Addison's  disease).  Negative  results 
were  obtained  in  18  syphilitics.  They  look  upon  a  positive  reaction 
as  indicative  of  active  tuberculosis.  Stimson^°  (1915),  who  gives  a  fairly 
exhaustive  table  of  recent  literature,  report;s  a  small  number  of  cases 
using  a  variety  of  antigens  but  his  results  are  inconclusive.  Craig^ 
(1915)  reports  the  results  of  examination  of  166  cases  of  pulmonary 
tuberculosis,  using  as  antigen  an  alcoholic  extract  of  several  strains  of 
human  tubercle  bacilli  which  had  grown  on  a  liquid  medium  of  alkaline 
bouillon  containing  egg,  with  96.2  per  cent  positive  results  in  active 
cases  and  66.1  per  cent  positive  in  inactive  cases.  One  hundred  and  fifty 
cases  of  syphilis  only  gave  2  positive  reactions  and  on  further  examina- 
tion these  revealed  lesions  in  the  lungs.  One  hundred  other  diseases 
were  examined  and  all  gave  negative  results.  These  results  are  certainly 
wonderful,  but  it  remains  for  future  investigators  to  corroborate  Craig's 
findings  and  prove  this  antigen  to  be  specific. 

As  noted  from  a  study  of  the  literature  a  large  number  of  antigens 
have  been  used,  but  the  most  reliable  investigators  all  concede  that  a  sus- 
pension of  living  tubercle  bacilli  is  the  only  antigen  of  specific  value  and 
with  the  fewest  objections.  The  objections  to  the  bacillary  emulsion  are 
the  small  limit  between  the  antigenic  and  anticomplementary  dose,  the 
turbidity  produced  in  the  tubes,  and  the  fairly  high  percentage  of  non- 
specific reactions.  In  the  hope  of  overcoming  these  difficulties,  and  also 
imitating  the  liberation  of  antigenic  materials  as  it  occurs  in  the  animal 
organism,  it  was  decided  to  try  to  obtain  the  antigen  from  the  tubercle 
bacillus  by  processes  as  nearly  identical  to  those  that  occur  in  the  body 
as  possible.  With  this  in  mind  and  realising  that  bacterial  antigens  are 
probably  of  protein  character,  the  following  investigations  were  carried 
out. 

In  order  to  determine  the  most  favorable  condition  for  the  liberation 
of  the  antigenic  products  from  the  tubercle  bacillus,  heavy  suspensions 
of  living  tubercle  bacilli  of  the  human  type  were  made  in  sterile  tubes 
and  with  sterile  physiological  salt  solution.  One  set  of  tubes  was  incu- 
bated, another  set  was  kept  at  room  temperature,  and  a  third  set,  as 
control,  was  heated  for  thirty  minutes  in  a  boiling  water  bath  to  kill 
the  bacilli  and  then  incubated.  The  criterion  used  for  determining  the 
disintegration  of  the  bacilli  was  the  amount  of  non-coagulable  nitrogen 
liberated  by  the  Folin  micro-method.  A  typical  set  of  these  results  is 
plotted  in  Chart  I.* 

There  is  a  gradual  liberation  of  non-eoagulable  nitrogenous  sub- 

20.  A.  M.  Stimson.     Bull.  U.  S.  M.  H.  &  P.  H.  Serv.,  No.  101,  pp.  7-29. 

21.  Charles  P.  Craig.     Amer.  Jour.  Med.  Sci.,  1915,  CL.,  pp.  781-790. 

*  Note. — The  complete  experimental  data,  methods  and  results  of  this  investigation  will  be 
reported  in  a  subsequent  paper. 


H.    J.    CORPEE,   M.D. 


107 


/ 

\, 

/ 

/ 

\ 

/ 

/ 

/ 

,-■ 

--'' 

/■' 

/ 

\ 

/ 

^^\ 

,-- 

'-" 

~^~ 

^^ 

[>^ 

^^^ 

stances  from  the  tubercle  bacillus,  as  noted  from  inspection  of  Chart  I, 
at  incubator  temperature  occurring  over  a  period  reaching  its  maximum 
at  about  the  eighth  day,  and  this  does  not  take  place  after  the  bacilli 
have  been  killed  by  heat.  At  room  temperature  this  does  not  occur  to 
an  appreciable  extent  within  that  period  of  time. 

CHART  I 

0.12 
0.11 
0.10 
0.09 
0.08 
0.07 
0.06 
0.05 
0.04 
0.03 
0.02 
0.01 
0.00 

MG.  0    12    3    4  5    6    7  8    9101112   Days 
N.    Continuous  Line  Heated  &  Incubated  Control. 
Dotted  Line  Incubated  Aseptic. 
Dash  Line  Room  Temp.  Aseptic. 

CHART H 

0.16 
0.15 
0.14 
0.13 
0.12 
0.11 
0.10 
0.09 
0.08 
0.07 
0.06 
0.05 
0.04 
0.03 
0.02 
0.01 
0.00 

MG.O    12    3    4  5    6    7   8    9  10111213141516   Days 
N.    Continuous  Line  Aseptic  Autolysis  in  Incubator. 

Dotted  Line  is  Antiseptic  (Toluene")  Autolysis  in  Incubator. 

The  process  by  which  these  nitrogenous  materials  appeared  was  next 
studied.  It  is,  of  course,  conceivable  that  it  might  be  either  a  simple 
dissolving  out  of  endogenous  nitrogenous  materials  from  the  bacilli  or 
it  may  be  the  result  of  enzyme  action,  an  autolysis.  As  shown  by  "Wells 
and  Corper^^  toluene  will  destroy  the  tubercle  bacilli  but  leaves  the 


— 

/ 

\ 

/ 

1 

\ 

/ 

1 

^ 

^ 

/ 

/ 

/ 

/ 

/ 

/ 

/ 

; 

/ 

/ 

y 

/ 

/ 

/ 

, 

■ 

/ 

/' 

/ 

.-'-'V 

^i 

1 

i 

22.  H.  G.  Wells  and  H.  J.  Corper.     Jour.  Infect.  Dis.,  Vol.  XI,  1912,  pp.  288-296. 


108 


COMPLEMENT   FIXATION   IN   TUBERCULOSIS 


enzymes  intact.  Chart  II  gives  the  findings  when  an  aseptic  and  anti- 
septic (toluene)  experiment  are  carried  out  at  incubator  temperature. 
From  this  experiment  it  can  be  concluded  that  autolysis  of  tubercle 
bacilli  occurs,  being  perceptible  at  about  the  second  or  third  day  and 
reaching  a  maximum  at  about  the  sixth  to  eighth  day  at  incubator 
temperature. 

The  above  experiments  have  also  been  repeated  using  bovine  tubercle 
bacilli,  and  the  same  is  found  to  hold  true. 

Now  that  it  is  proven  that  the  tubercle  bacillus  autolyzes,  the  next 
and  most  important  question  concerning  us  is  whether  this  autolysis 
has  any  relation  to  the  increase  of  antigenic  strength  in  the  autolysate. 
In  order  to  test  this  the  autolysate  from  a  series  of  suspensions  of 
tubercle  bacilli  in  sterile  physiological  salt  solution  were  tested  coinci- 
dently  at  definite  intervals  for  non-coagulable  N  content  and  titrated 
for  antigenic  strength.  The  latter  was  done  by  titrating  varying 
amounts  of  the  antigen  against  a  four-plus  tuberculosis  serum  and  noting 
the  amount  of  complement  fixation  obtained. 

CHARTm 


Correlation 

of  Autolysis  and  Antigen  Formation. 

Nitrogen  Curve 

Antigen  Curve 

D/ikYS 

MG.  N.  PER  C  C 

0,2CC 

0,ICC 

0,5CC 

OjOlCC 

0,005CC 

O.OOICC 

0,0005CC 

0,OOOICC 

0 

0.00 

-I--H- 

+  +  -f- 

-|--f--h 

— 



— 

— 

— 

1 

0.00 

+  +  + 

+  f  + 

+  +  + 

+ 



— 



— 

2 

0.01 

+  +  + 

++> 

+,d-  + 

+  -I-4- 

+ 

— 

— 

— 

3 

0.02 

+  +-I- 

t-+  + 

+  +■>- 

4--,+  + 

-h+i- 

-t-     + 

+ 

— 

4 

0.03 

+  +  + 

+  +  + 

-I-  +  + 

+  +> 

+-±  + 

+  +  + 

+ 

+ 

6 

0.05 

+  +  + 

-I-+-I- 

+  +  + 

+  +  + 

+  +~4^ 

■^-rf + 

+       -H 

-h    + 

8 

0.06 

+  +  + 

++  + 

+  +  + 

+  -h-t- 

+  +  -1- 

+  H-  + 

-!-  +  + 

+    + 

10 

0.08 

+  +  + 

-t-+  + 

+  +  + 

+  +  + 

+  +  + 

-1-,H-  + 

4-+  + 

+ 

13 

0.15 

+  +H- 

-t— f--f 

-1-  -I-  + 

-I-  +  + 

+  +  + 

+  M-  4- 

+-I-4- 

+    + 

As  seen  from  Chart  III  (the  dotted  line  joins  the  minimum  concen- 
trations which  give  a  four-plus  reaction)  although  the  nitrogen  figures 
and  the  antigenic  titer  do  not  exactly  increase  parallel  there  is  a 
certain  relation  between  them,  and  it  is  to  be  noted  that  an  antigenic 
titer  of  0.1  c.c.  on  the  first  day  becomes,  gradually  and  consistently,  a 
titer  of  0.001  c.c.  on  the  sixth  day.  Thus  the  autolysate  from  suspen- 
sions of  living  virulent  tubercle  bacilli  becomes  stronger  in  antigenic 
titer  coincident  with  the  occurrence  of  autolysis. 

In  order  to  test  the  value  of  the  autolysate  antigen  it  was  compared 
in  a  large  series  of  cases  (over  600)  with  the  bacillary  emulsion.  In  a 
general  way  it  can  be  stated  that  the  autolysate  antigen  possesses  the 
following  advantages  over  the  bacillary  emulsion:  it  has  a  much  larger 
range  between  the  antigenic  and  anticomplementary  dose  (even  0.2  c.c. 
of  0.001  c.c.  strength  has  no  anticomplementary  effect)  ;  it  does  not 
lose  its  titer  when  kept  on  ice  (several  autolysates  have  kept  their  titer 
for  four  months)  ;  it  produces  no  interfering  turbidity  in  the  hemolytic 


H.    J,    CORPER,    M.D. 


109 


system;  and  it  is  more  specific  than  the  bacillary  emulsion.  Although 
more  than  600  examinations  were  made,  using  the  bacillary  emulsion 
and  autolytic  antigens,  for  the  sake  of  accurate  comparison  only  the 
results  from  361  cases  are  given  in  tabulated  form  because  only  such 
cases  were  included  in  this  tabulation  as  were  worked  up  accurately 
from  the  clinical  standpoint.  Wherever  there  existed  any  question  as  to 
the  accuracy  of  diagnosis  or  where  all  the  clinical  facts  did  not  agree 
perfectly  the  case  was  discarded  for  this  purpose.  The  results  obtained 
are  given  in  Chart  IV. 

CHAET  IV 


Patients 
Exam- 
ined 

Number 
of  Exam- 
inations 

Neg- 
ative   E. 
Results 

Neg- 
ative A. 
Results 

Positive 

E. 
Results 

Positive 

A. 
Results 

Sputum 

V.  P. 

Non 

T.B 

25 

26 

lA 
19 
23 

19 
24 

6 

2* 

7 
2* 

25- 

1-  11+ 

Quest 

Non  T.B.... 

11 

11 

5 
6 

7 
9 

6 
5 

4 
2 

11- 

3-     6+ 

Incip 

Inact 

47 

50 

2A 
30 
39 

35 
43 

18 
9 

15 
7 

46— 1-f 

Incip 

Act 

27 

30 

5A 
10 
18 

14 
23 

15 
7 

16 
7 

19-7+ 

M.A 

Inact 

12 

14 

8 
10 

9 
13 

6 

4 

5 

1 

6—6+ 

M.A 

Act 

47 

55 

8A 
13 
24 

27 
37 

34 
23 

28 
18 

12-34+ 

F.A 

Inact 

5 

5 

3 

4 

3 
4 

2 

1 

2 

1 

3-2+ 

F.A 

Active 

187 

216 

28A 
81 
112 

lA 
110 
155 

107 
76 

105 
60 

15—172+ 

Totals 

361 

407 

213 
280 

225 
309 

194 
127 

182 
98 

Light  figures  designating  +  and  stronger  positives. 
Heavy  figures  designating  ++  and  stronger  positives. 

It  is  to  be  noted  that  the  cases  are  divided  according  to  the 
National  Association  classification,  and  that  the  results  are  given 
as:  Neg.  E. — ^negative  results  with  bacillary  emulsion;  Neg.  A. — 
negative  autolysate ;  Positive  E. — positive  bacillary  emulsion,  and  Posi- 
tive A — positive  autolysate.  Under  sputum  are  given  the  findings  for 
tubercle  bacilli  in  the  sputum,  while  under  V.  P.  are  given  the  results  of 


*  Note. — One  of  these  cases  had  received  a  tuberculin  injection  for  diagnostic  purposes  a  short 
time  previous  to  drawing  the  blood. 


110  COMPLEMENT  FIXATION  IN   TUBERCULOSIS 

von  Pirquet  tests  in  the  questionable  and  non-tuberculous  cases  (it  is 
significant  that  all  von  Pirquet  negatives  in  our  series  gave  negative 
fixation  tests).  The  complement  fixation  findings  with  the  baeillary 
emulsion  are  given  in  two  figures,  the  upper  black  figure  representing  the 
findings  if  a  single  plus  is  considered  a  positive  reaction  (the  extreme 
upper  figure  followed  by  an  A  designates  an  anticomplementary 
result,  a  large  predominance  of  these  are  noted  under  the  baeillary 
emulsion  results),  while  the  lower  red  figure  represents  the  findings  if 
a  double  plus  is  considered  positive.  Using  a  single  plus  as  criterion 
a  higher  percentage  of  positive  results  is  obtained  in  the  non-tuberculous 
and  also  in  the  more  advanced  cases.  The  double  plus  criterion  is,  how- 
ever, preferred  since  it  seems  to  give  us  the  more  accurate  view  of  the 
state  of  affairs  (and  is  the  same  criterion  used  for  making  a  plus  Wasser- 
mann  diagnosis),  giving  a  low  percentage  positive  in  normals  but  also 
lowering  the  positive  findings  in  the  clinically  certain  tuberculosis  cases. 
Briefly  stated,  the  findings  may  be  summed  up  as  follows  (considering 
only  double-plus  reactions  as  positive)  :  Only  1  non-tuberculous  case  out 
of  25  gave  a  positive  reaction  (96  per  cent,  negative)  (the  second  posi- 
tive having  received  a  tuberculin  injection  a  short  time  previous  to 
making  the  test)  by  both  tests ;  on  questionable  non-tuberculous  cases 
18  per  cent,  gave  an  autolysate  test  while  45.5  per  cent,  gave  an  emul- 
sion test;  incipient  inactive  cases  gave  14  per  cent,  positive  reactions 
with  the  autolysate  and  18  per  cent,  with  the  emulsion ;  incipient  active 
eases  gave  the  same  with  both — 23.3  per  cent,  reactions;  moderately 
advanced  inactive  cases  gave  7.15  per  cent,  with  the  autolysate  and  28.6 
per  cent,  with  the  emulsion,  while  the  active  cases  gave  37.7  per  cent, 
with  the  autolysate  and  41.8  per  cent,  with  the  emulsion;  the  far 
advanced  inactive  cases  gave  20  per  cent,  reactions  in  both  cases,  while 
the  active  cases  gave  27.6  per  cent,  with  the  autolysate  and  35  per  cent, 
with  the  emulsion.  A  greater  percentage  of  reactions  is  always  obtained 
in  the  active  cases,  but  the  results  seem  to  indicate,  as  was  pointed  out  by 
Fraser,*  that  antibodies  in  free  form  capable  of  binding  antigen  are 
apparently  not  always  present  in  the  sera  of  tuberculous  individuals, 
but  they  are  more  liable  to  be  present  in  the  active  form  of  the  disease. 

Now  we  may  ask :  Has  the  complement  fixation  test  for  tuberculosis 
any  practical  value  for  diagnosis?  Its  value  lies  in  the  fact  that  when 
it  is  positive  it  practically,  taken  in  conjunction  with  other  findings, 
makes  the  diagnosis  of  tuberculosis  definite.  It  is  of  value  also  from  a 
differential  diagnostic  standpoint  in  pointing  out  tuberculosis  when 
positive  as  against  syphilis,  abscess  of  the  lung,  empyema  from  other 
causes,  carcinoma,  bronchiectasis,  etc. 

Now  that  the  complement  fixation  test  for  tuberculosis  has  been  found 
to  be  lacking  in  the  point  of  percentage  efficiency  as  a  diagnostic  test 
for  tuberculosis,  is  it  possible  to  further  study  the  phenomenon  with  a 
view  to  making  a  more  efficient  test  and  correcting  some  of  the  possible 
deficiencies  in  the  method  as  applied  to  the  above  investigation?  The 
improvements  suggested  by  the  above  investigation  and  which  are  at 

*  Loc.  cit. 


H.    J.    CORPER,    M.D.  Ill 

present  being  tried  in  our  laboratories  are  the  following :  With  a  view  to 
obtaining  a  higher  percentage  positive  results  a  number  of  autolysates 
prepared  from  different  strains  of  virulent  tubercle  bacilli  are  being 
tested  on  the  same  sera  in  order  to  prove  whether  a  polyvalent  autolysate 
antigen  would  be  more  efficient  than  a  monovalent  antigen;  sera  are 
being  drawn  at  various  intervals  during  the  day  to  see  whether  there  is 
a  more  opportune  time  for  obtaining  the  antibodies  in  the  sera,  this 
being  suggested  by  the  periodicity  of  the  temperature  curve  (weekly 
intervals  are  also  being  considered)  ;  and,  finally,  antigen  and  antibody 
tests  are  being  made  coincidently  on  the  same  sera,  as  it  has  been  sug- 
gested that  possibly  in  the  absence  of  antibodies  a  test  for  antigen  may 
give  results.* 

SUMMAEY 

1.  Virulent  cultures  of  tubercle  bacilli  free  from  all  foreign  sub- 
stances suspended  in  sterile  salt  solution  undergo  autolysis  at  incubator 
temperature  as  indicated  by  the  liberation  of  nitrogenous  substances, 
reaching  a  maximum  at  about  the  sixth  to  eighth  day. 

2.  During  this  autolysis  of  virulent  cultures  of  tubercle  bacilli  there 
is  a  coincident  liberation  of  antigenic  substances  suitable  for  complement 
fixation  for  tuberculosis.  This  autolysate  antigen  possesses  advantages 
over  a  suspension  of  living  virulent  tubercle  bacilli  as  an  antigen  for 
complement  fixation  tests. 

3.  As  a  result  of  the  examination  of  361  patients,  using  both  an 
emulsion  and  autolysate  prepared  from  living  virulent  human  tubercle 
bacilli  as  antigens,  25  normals,  11  questionable  non-tuberculous  and  325 
definitely  tuberculous  cases  it  can  be  stated  that : 

(a)  The  complement  fixation  test  for  tuberculosis  is  not  an  absolute 
test,  being  positive  only  in  about  30  per  cent  of  all  the  clinically  definite 
cases  of  tuberculosis  both  active  and  inactive.  Active  cases  give  a 
higher  percentage  positive  results  than  inactive  cases. 

(b)  The  value  of  the  complement  fixation  test  for  tuberculosis  lies 
in  the  fact  that  when  the  test  is  definitely  positive  it  practically,  taken  in 
conjunction  with  other  findings,  makes  the  diagnosis  of  tuberculosis 
definite. 

(c)  It  is  of  value  also  from  a  differential  diagnostic  standpoint  when 
the  diagnosis  is  obscure  in  indicating  tuberculosis  when  positive  as 
against  syphilis,  carcinoma,  abscess  of  the  lung,  empyema  from  other 
causes  than  the  tubercle  bacillus,  bronchiectasis,  etc. 

4.  The  practical  absence  of  the  reaction  in  non-tuberculous  cases 
makes  this  test,  when  positive,  of  far  greater  value  in  the  diagnosis  of 
tuberculosis  than  any  of  the  biological  tests  for  tuberculosis  thus  far 
discovered.  A  positive  test  was  never  obtained  in  the  absence  of  a  von 
Pirquet  test  while  a  large  percentage  of  positive  von  Pirquet's  in  normal 
individuals  gave  negative  fixation  tests. 


*  Note. — In  conclusion  I  wish  to  express  my  appreciation  to  Mr.  H.  C.  Sweaney  and 
Dr.  M.  Marshak  for  their  assistance  in  carrying  ont  this  work,  and  to  Dr.  J.  W.  Coon  and 
the  doctors  of  the  Municipal  Tuberculosis  Sanitarium  for  their  kind  co-operation. 


TUBERCULOSIS   OF   THE   KIDNEY 

By  Herman  L.  Kretschmer,  M.D. 

CHICAGO 

Tuberculosis  of  the  kidney  is  one  of  the  lesions  of  the  higher  urinary 
tract  that  has  often  been  described  as  being  difficult  to  diagnose.  This 
traditional  statement  has  been  handed  down  from  one  author  to  another 
over  a  period  of  many  years.  The  recent  advances  in  genito-urinary 
diagnosis  have  proved  the  error  of  such  statements.  Tuberculosis  of 
the  kidney  is  of  much  more  frequent  occurrence  than  was  formerly 
supposed,  and  the  diagnosis  can  be  made  in  each  and  every  case. 

Perhaps  one  of  the  reasons  why  the  diagnosis  is  not  made  more  fre- 
quently is  that  it  is  not  thought  of  as  a  possibility.  The  persistence  of 
pus  in  the  urine,  especially  in  young  patients,  associated  with  fre- 
quency, and  possibly  painful  urination,  should  always  arouse  our  sus- 
picions. Very  often,  instead  of  attempting  a  diagnosis,  these  patients 
are  treated  for  cystitis,  pyelitis,  nephritis,  etc.  Even  when  the  diag- 
nosis of  renal  tuberculosis  is  made,  the  physician  remarks  that  the 
patient  has  not  lost  weight,  is  not  cachectic.  In  order  to  obtain  the  best 
possible  results,  a  diagnosis  must  be  made  long  before  these  symptoms 
supervene.  Tuberculosis  of  the  kidney  is  no  exception  to  the  rule  that 
the  earlier  the  diagnosis  is  made,  the  better  the  end  result. 

That  the  exact  opposite  may  be  true,  I  have  experienced  in  one  case, 
in  a  patient  who  had  an  active  tuberculosis  of  the  kidney.  Upon  medi- 
cal management  he  gained  thirty  pounds  in  weight  shortly  after  which 
he  developed  a  T.B.  epididymitis. 

Diagnosis  of  tuberculosis  of  the  genito-urinary  tract  can  very  often 
be  made  without  resorting  to  the  use  of  special  diagnostic  instruments. 
After  diagnosis  has  been  made,  special  instruments  must  be  used  to 
localize  the  site  of  the  lesion.  Not  infrequently  one  is  able,  as  a  part 
of  the  general  physical  examination,  to  obtain  evidence  of  tuberculosis 
in  other  parts  of  the  body,  for  example,  lung,  bone  or  lymph  glands. 
Without  resorting  to  the  use  of  special  instruments,  one  can  obtain  evi- 
dence of  tuberculosis  in  the  genital  tract.  A  nodule  in  the  epididymis 
or  seminal  vesicle,  a  hard,  nodular  infiltration  of  the  prostate,  coupled 
with  the  presence  of  pus  in  the  urine,  should  always  lead  to  the  pre- 
sumptive diagnosis  of  tuberculosis  until  the  cause  of  the  pyuria  and 
the  nature  of  the  previously  mentioned  nodules  and  infiltration  are 
established. 

In  women,  occasionally  the  vaginal  examination  may  give  us  infor- 
mation suggestive  of  T.B.  disease  of  the  kidney.  The  vaginal  examina- 
tion may  show  a  thick  and  enlarged,  hard  ureter.  Each  and  every 
ureter  that  one  is  able  to  palpate  through  the  vagina,  and  that  may 
be  hard  and  sensitive,  is  not  necessarily  of  tuberculous  origin.  In 
late  cases,  there  may  often  be  demonstrated  a  variable  degree  of  ten- 

112 


HERMAN   L.    KRETSCHMER,    M.D.  113 

derness  over  the  bladder.  Occasionally  one  is  able  to  demonstrate  the 
presence  of  a  renal  tumor. 

A  great  deal  of  care  must  be  exercised  in  interpreting  a  renal  tumor. 
One  cannot  always  tell,  from  the  amount  of  tenderness  and  the  shape 
of  the  tumor,  its  exact  nature.  Indeed,  the  pain  and  enlargement  not 
infrequently  are  found  on  the  normal  side,  whereas  the  tuberculous  kid- 
ney is  not  tender  nor  palpable.  The  danger,  without  further  proof  of 
the  nature  of  the  enlarged  kidney,  under  such  circumstances,  is  plain. 
The  dangers  of  removing  the  normal  kidney  and  leaving  the  tuberculous 
one  behind  are  self-evident. 

The  absolute  diagnosis  of  tuberculous  infection  of  the  urinary  tract 
must  depend  upon  the  demonstration  of  the  tubercle  bacillus  in  the 
urine. 

The  older  writers  upon  this  subject  recorded  the  rarity  with  which 
they  were  able  to  demonstrate  the  tubercle  bacillus.  More  recent  pub- 
lications, however,  present  a  much  larger  percentage  of  positive  results. 
In  the  last  sixty  cases,  we  have  been  able  to  demonstrate  the  tubercle 
bacillus  in  all  but  three  cases  on  the  stained  slide. 

The  statement  has  been  repeatedly  made  that  it  is  difficult  to  dem- 
onstrate tuberculosis  in  those  cases  associated  with  profuse  hemorrhage. 
I  have  seen  one  such  case  in  which  we  found  bacilli.  In  order  to  dem- 
onstrate the  presence  of  the  T.B.  in  the  urine,  it  is  necessary  that  the 
urine  used  for  examination  come  from  both  kidneys.  In  the  rarer 
cases  in  which  a  stricture  of  the  ureter  exists,  as  a  result  of  which  no 
urine  finds  its  way  into  the  bladder,  one  would  not  be  able  to  dem- 
onstrate the  tubercle  bacillus. 

The  demonstration  of  tubercle  bacilli  in  the  urine  leads  to  the  ques- 
tion of  determining  the  origin  of  the  organisms.  One  should  not  forget 
that  the  organisms  may  come  from  the  vesicles  and  prostate.  In  other 
words,  because  bacilli  are  found  in  the  urine  one  should  not  come  to 
the  conclusion  that  they  have  their  origin  in  the  kidney. 

Although  one  may  not  be  able  to  demonstrate  the  tubercle  bacillus 
in  the  urine  after  a  few  examinations,  if  the  presence  of  the  pyuria 
continues,  the  search  is  usually  given  up.  In  some  of  these  cases  cul- 
tures, of  the  urine,  when  made,  fail  to  reveal  the  presence  of  organisms. 
A  persistent  pyuria  with  negative  cultures  should  always  arouse  our 
suspicions  that  we  are  possibly  dealing  with  a  T.B.  In  these  cases, 
it  might  be  well  to  resort  to  the  guinea  pig  before  doing  a  nephrectomy. 

The  amount  of  pus  found  in  the  urine  is  quite  variable.  It  was 
formerly  taught  that  patients  suffering  from  T.B.  of  the  kidney  always 
had  large  quantities  of  pus  in  the  urine.  It  is  but  natural  to  expect 
that  the  amount  of  pus  in  the  urine  may  vary  within  wide  limits.  In 
two  of  our  cases,  in  which  large  clumps  of  pus  were  found  at  the  first 
examination,  the  urine  at  the  subsequent  examination  was  clear,  and 
showed  but  a  few  pus  cells  under  the  microscope,  so  that  the  fact  that 
urine  is  clear  and  contains  but  a  few  leucocytes  is  no  argument  against 


114  TUBERCULOSIS   OP   THE   KEDNBY 

the  presence  of  T.B.  Not  always  is  the  urine  of  the  tuberculous  kid- 
ney also  sterile  upon  ordinary  culture  examination.  In  most  of  our  eases 
we  found  the  bacillus  coli.  The  presence  of  the  bacillus  coli  may  for 
a  time  mask,  as  it  were,  the  tubercle  bacillus.  At  the  present  time  a  good 
deal  of  work  is  being  done  on  the  treatment  of  colon  pyelitis  by  lavage 
of  the  renal  pelvis.  One  of  the  thoughts  which  should  be  uppermost 
in  our  minds,  when  carrjdng  out  this  form  of  treatment,  is  whether 
or  not  the  colon  may  not  be  associated  with  a  tuberculosis.  This,  par- 
ticularly, in  the  early  cases  without  the  involvement  of  the  bladder. 
The  danger  of  coming  to  wrong  conclusions  under  such  circumstances 
is  evident. 

In  cases  in  which  the  tubercle  bacilli  cannot  be  demonstrated  in 
microscopic  slides,  it  becomes  necessary  to  resort  to  the  use  of  the 
guinea  pig.  It  is  needless  to  say  that  very  often  pigs  are  injected  simply 
to  exclude  tubercle  bacilli,  not  because  one  is  suspected.  A  great  deal 
of  care  must  be  taken  in  carrying  out  this  work,  as  there  are  many 
possible  sources  of  error.  The  value  in  cases  in  which  a  few  organisms 
are  present  is  apparent.  The  guinea  pig  has  uniformly  given  us  good 
results,  which  experience  coincides  with  the  experience  of  others.  Ten- 
ney,  Barney,  and  Young  and  others  have  recorded  failures  to  obtain 
proof  from  the  pig  in  positive  cases.    We  have  but  one  failure. 

In  performing  the  guinea  test,  it  is  essential  that  urine  from  the  in- 
fected kidney  be  obtained.  In  other  words,  where  the  ureter  is  obKt- 
erated,  the  guinea  pig  test  will  fail.  The  more  accurate  way  would  be 
to  use  two  guinea  pigs  and  to  inject  the  right  side  into  one  pig  and  the 
left  side  into  another. 

The  various  methods  of  injection  need  be  mentioned  but  briefly: 
intrasplenic,  intrahepatic  and  subcutaneous,  either  with  or  without 
previously  crushing  the  regional  lymph  nodes  as  suggested  by  Block. 
A  subcutaneous  injection  after  crushing  the  lymph  nodes  has  given  us 
the  best  results,  although  this  method  has  been  open  to  criticism  that 
should  the  pig  have  tubercle  bacilli  in  its  system  they  would  localize 
here.  The  objections  to  the  guinea  pig  test  are  that  it  requires  a 
certain  amount  of  time  before  one  obtains  the  evidence;  and,  second, 
that  the  pigs  may  die  before  the  tuberculous  lesions  have  had  time  to 
develop.  That  one  must  resort  to  many  pigs  I  have  experienced  in  one 
case  in  which  nine  pigs  were  injected,  solely  for  the  purpose  of  exclud- 
ing T.B.  One  must  be  rather  cautious  in  his  interpretation  of  guinea  pig 
findings.  Because  a  pig  dies  of  tuberculosis  does  not  necessarily  mean 
that  the  patient  from  whom  the  urine  was  obtained  necessarily  suffers 
from  tuberculosis  of  the  kidney.  Much  discussion  has  taken  place  upon 
this  point,  many  authors  contending  that  if  a  patient's  urine  contains 
tubercle  bacilli  the  patient  is  a  sufferer  from  renal  tuberculosis.  In 
other  words,  that  a  normal  kidney  does  not  excrete  tubercle  bacilli. 
There  are  others  who  maintain  that  tubercle  bacilli  may  be  excreted 
without  the  patient  having  tuberculosis  of  the  kidney.     It  has  heen 


HERMAN   L.    KEETSCHMER,    M.D.  115 

repeatedly  stated  that  in  order  to  make  a  positive  case  of  T.B.  of  the 
kidney  one  must  find  the  presence  of  pus  beside  the  tubercle  bacilli. 
It  is  also  a  well-known  fact  that  kidneys  have  been  removed,  in  the  urine 
of  which  T.B.  have  been  demonstrated  and  examination  of  the  speci- 
mens after  operation  reveal  the  presence  of  stone  or  tumor.  The  sub- 
sequent examination  of  the  urine  failed  to  reveal  the  presence  of  bacilli. 
Whether  or  not  this  state  of  affairs  exists  only  on  one  side,  because  of 
the  associated  pathological  condition,  still  remains  unsolved.  That  a 
patient  may  excrete  T.B.  from  both  sides  without  the  presence  of  pus, 
I  can  vouch  for,  having  seen  one  such  case. 

Use  of  the  tuberculin  reaction  as  a  diagnostic  aid  in  the  diagnosis 
of  tuberculosis,  I  have  never  resorted  to. 

Special  Methods  op  Diagnosis 

After  demonstrating,  beyond  any  question  of  doubt,  the  fact  that 
a  patient  has  T.B.,  the  next  problem  for  consideration  is  to  determine 
its  location.  This  can  be  definitely  established  in  the  largest  majority 
of  cases  by  means  of  the  cystoscopic  examination  and  ureteral  cathe- 
terization. There  has  always  been  more  or  less  objection  on  the  part 
of  certain  men  to  this  method  of  diagnosis,  because  of  so-called  dangers, 
which  it  seems  to  me  are  more  theoretical  than  real.  Cystoscopic  exam- 
inations and  ureteral  catheterization  is  of  definite  advantage  in  giving 
us  information  relative  to  the  condition  of  the  bladder,  whether  or  not 
it  is  involved,  and  the  extent  of  its  involvement.  Further  information 
is  obtained  relative  to  the  pathological  side,  and  to  the  functional 
capacity  of  the  kidney,  which  question  is  of  serious  moment  when  con- 
templating a  nephrectomy. 

There  are  two  conditions  under  which  a  plain  cystoscopic  examina- 
tion gives  us  no  information  and  they  are :  First,  the  very  early  cases, 
before  there  is  any  involvement  of  the  bladder,  in  other  words  in 
which  the  bladder  is  normal;  and,  second,  in  the  very  advanced  eases 
in  which  cystoscopic  examination  cannot  be  carried  out.  These  cases 
will  be  discussed  in  a  group  by  themselves. 

•  Many  significant  changes  are  those  occurring  around  the  ureteral 
orifice  which  may  be  in  the  nature  of  a  hyperemia  or  oedema.  Later,  the 
edges  of  the  ureter  become  rigid  and  gaping,  finally  producing  a  retrac- 
tion and  ulceration.  Attention  has  been  repeatedly  called  to  the  irreg- 
ular distribution  of  areas  of  cystitis ;  and  so-called  patch  cystitis  as  being 
suggestive  of  T.B.  In  cases  in  which  changes  have  occurred  around 
the  ureteral  orifice,  one  may  venture  the  diagnosis  of  T.B.  If  the  oppo- 
site ureter  is  normal  and  under  certain  circumstances  pathological, 
one  may  not  always  be  in  a  position  to  give  a  definite  expression  of 
opinion  relative  to  the  kidney  so  that  it  is  imperative  to  catheterize  the 
ureters.  The  former  teachings  were  that  one  should  catheterize  only 
the  diseased  side,  which,  of  course,  would  leave  us  in  the  dark  about  the 
well  side.  The  kidney  which  is  to  remain  must  be  a  well  studied  and 
worked  out  problem. 


116  TUBERCULOSIS   OF   THE   KIDNEY 

One  is  always  desirous  of  knowing  whether  the  T.B.  is  unilateral 
or  bilateral.  In  cases  where  there  is  any  doubt,  we  have  resorted  to 
guinea  pig  inoculations. 

Diagnostic  Excision  op  Tissue  from  the  Bladder  Through 

THE  CysTOSCOPE 

The  employment  of  this  method  in  diagnosis  of  tuberculosis  of 
the  kidney  was  recently  suggested  by  Buerger,  and  may  be  of  distinct 
value  in  certain  obscure  cases.  It  is  not  suggested  that  this  form  of 
diagnosis  should  be  a  substitute  for  the  regular  well  recognized  diag- 
nostic procedures,  nor  should  it  be  used  as  a  short  cut  to  diagnosis. 
Nevertheless,  it  is  quite  possible  to  employ  this  method  when  other 
methods  fail.  This  has  served  us  in  one  case,  where  the  bacilli  could 
not  be  found,  nor  could  we  see  a  normal  ureter.  Around  the  patho- 
logical ureter  were  seen  areas  of  edema  and  granulation  tissue.  (Lee 
Kind.) 

X-Rays 

The  value  of  the  employment  of  X-Rays  in  the  diagnosis  of  this 
condition  must  naturally  be  limited  to  the  advanced  cases,  and  hence  its 
value  can  never  be  very  great,  as  an  early  diagnosis  is  the  all-important 
factor  in  this  condition.  It  is  conceivable,  however,  that  in  some  of  the 
late  cases  in  which  cystoscopy  cannot  be  carried  out,  and  in  which 
destruction  of  the  kidney  with  its  associated  changes  has  occurred  may 
be  recognized  on  the  X-Ray  plate.  The  so-called  Kittniere,  of  the  Ger- 
mans, has  been  recognized  in  this  manner  several  times.  The  danger 
of  error  in  this  method  of  diagnosis  results  from  trying  to  diagnose 
too  much  from  the  plate  and  without  taking  into  consideration  the  gross 
clinical  evidence.  Tuberculosis  of  the  kidney,  with  positive  plate  find- 
ings, is  frequently  confused  with  stone.  The  calcified  areas  in  T.B., 
however,  are  never  so  sharp  and  clear  cut  as  the  shadows  produced 
by  stones.  The  edges  usually  fuse  into  the  surrounding  tissue.  These 
areas  of  calcification  are  usually  found  in  the  parenchyma. 

Pyelography 

As  a  routine  in  our  diagnostic  work,  we  have  not  employed  pye- 
lography. If  one  uses  pyelography  subsequent  to  the  diagnostic  meas- 
ures as  taken  up  in  their  order  in  this  paper,  one  does  not,  as  a  rule, 
obtain  much  additional  information,  nor  does  it  alter  the  treatment.  It 
has  been  repeatedly  stated  that  pyelography  in  these  cases  would  be 
more  dangerous  than  in  other  kidney  conditions. 

There  still  remain  a  few  cases  which,  for  various  reasons,  cannot 
be  diagnosed  by  one  or  several  of  the  previously  considered  diagnostic 
measures.  These  are  usually  in  the  very  advanced  or  late  cases,  patients 
in  whom  cystoscopy  and  ureteral  catheterization  are  impossible.  If, 
however,  a  diagnosis  of  T.B.  of  the  higher  urinary  tract  has  been  made. 


HERMAN    L.    KEETSCHMER^    M.D.  117 

and  all  methods  of  diagnosis  have  been  exhausted  without  making  a 
diagnosis,  it  might  become  necessary  to  resort  to  some  surgical  opera- 
tion to  determine  whether  the  process  is  present  on  one  or  both  sides. 

Bilateral  exploratory  operations  have  been  suggested  by  many  kid- 
ney surgeons.  This  method  of  exploration  has  been  open  to  criticism; 
although  the  supposedly  healthy  kidney  has  been  explored  and  its  ureter 
and  external  appearance  found  normal,  one  cannot  be  positive  that  a 
T.B.  is  not  present. 

It  seems  to  me  a  much  more  logical  method  of  procedure  would  be 
an  extra-peritoneal  dissection  of  the  ureter  on  the  well  side,  the  per- 
formance of  ureterostomy  and  inserting  a  catheter  into  this  ureter  for 
the  purpose  of  obtaining  urine  for  study  from  the  supposedly  normal 
kidney. 

Differential  Diagnosis 

Usually  not  much  difficulty  is  experienced  in  excluding  other  lesions 
of  the  urinary  tract.  Difficulty  may  arise,  as  previously  mentioned 
when  stone  and  T.B.  occur  in  the  same  kidney.  Gall  stones  but  rarely 
have  been  confused.  Appendicitis,  on  the  other  hand,  quite  frequently. 
A  few  weeks  ago  I  saw  two  eases  in  one  week;  these  patients  had  been 
operated  on  for  appendicitis,  although  both  had  tuberculosis  of  the 
kidney.  Occasionally,  in  young  individuals  suffering  from  renal  tumor. 
a  differentiation  from  tuberculosis  may  be  in  order. 

Treatment 

I  will  consider  only  the  surgical  treatment,  as  you  are  all  familiar 
with  the  various  diatetic,  hygienic  and  serological  methods  of  treat- 
ment of  tuberculosis  in  general.  Xor  will  I  take  up  your  time  by  going 
into  the  details  of  the  surgical  technique. 

Indications  for  Nephrectomy 

Not  only  has  the  mortality  rate  been  very  materially  reduced  and 
the  operative  results  markedly  improved  because  of  the  institution  of 
early  diagnosis,  but  also  because  of  the  institution  of  nephrectomy 
at  a  much  earlier  period  in  the  disease  than  formerly.  Formerly,  the 
patients  were  subjected  to  operation  only  when  there  were  either  marked 
systemic  disturbances,  such  as  loss  of  weight  and  strength,  high  fever. 
profuse  bleeding  and  great  urinary  distress.  At  the  present  time  these 
patients  are  operated  upon  very  early  in  the  course  of  the  disease,  long 
before  it  has  advanced  far  enough  to  undermine  the  general  health  of 
the  patient.  The  greatest  plea  for  an  early  operation  is  that  based 
upon  an  analysis  of  the  operative  results.  The  early  cases  show  a  com- 
plete restoration  of  function,  which  diminishes  in  direct  ratio  to  the 
duration  of  the  disease. 

Chetwood  sums  up  this  subject  very  well  when  he  says.  '"The  assem- 
bled facts  indicate  that  the  tendency  of  tuberculosis  is  to  be  progres- 


118  TUBERCULOSIS   OF   THE   KIDNEY 

sive,  and  while,  as  a  rule,  in  the  beginning  only  one  kidney  is  involved, 
that  there  is  a  strong  tendency  later  on  to  implicate  the  other  organ; 
that  the  duration  of  life,  following  operation,  ranges  from  several 
months  to  what  would  seem  to  be  almost  a  permanent  cure ;  and  that 
the  operative  mortality  is  low. ' '  These  are  strong  arguments  in  favor  of 
early  operations,  when  tuberculosis  of  one  kidney  is  established. 

When  there  are  no  contra-indications,  nephrectomy  should  be  carried 
out  just  as  soon  as  the  diagnosis  has  been  definitely  established.  There 
is  not  much  to  be  gained  by  waiting,  or  by  instituting  non-operative 
forms  of  treatment,  except  in  those  cases  which  will  be  mentioned 
below. 

Contra-Indications 

Before  nephrectomy  is  undertaken,  the  remaining  kidney  must  be 
subjected  to  careful  study,  regarding  its  function,  in  order  to  determine 
its  ability  to  assume  the  added  burden  after  the  removal  of  the  dis- 
eased kidney.  It  is  also  important  to  demonstrate  the  presence  of  a 
second  kidney  before  removing  the  diseased  one.  Although  absence  of 
one  kidney  is  rare,  it  is  a  possibility  to  be  reckoned  with.  Disease  in  the 
opposite  kidney  is  not  always  a  contra-indication ;  for  example,  there 
may  be  present  in  the  opposite  kidney  a  calculus.  This  can  be  removed 
by  the  proper  operation  prior  to  undertaking  the  nephrectomy.  The 
so-called  toxic  albuminuria  has  been  noted  to  completely  disappear  after 
the  removal  of  the  diseased  kidney.  While  nephritis,  in  the  opposite 
kidney  may  not  be  an  absolute  contra-indication,  depending  in  part 
upon  its  extent  and  the  amount  of  disturbed  function,  the  prognosis  is 
not  as  good  under  these  conditions  as  it  would  be  if  the  opposite  kidney 
were  normal.  Tuberculosis  of  the  bladder  and  genital  organs,  both  for- 
merly considered  as  contra-indications,  are  no  longer  so  considered. 

In  cases  with  advanced  pulmonary  tuberculosis,  nephrectomy  may 
be  resorted  to  as  a  palliative  measure,  in  such  cases  associated  with  pro- 
fuse bleeding,  in  the  cases  associated  with  severe  renal  coUc,  and 
where  the  patient  is  suffering  from  marked  urinary  distress.  Not  infre- 
quently the  advisability  of  nephrectomy  is  questioned,  because  of  the 
poor  general  condition  of  the  patient.  That  is,  where  a  patient  is  suffer- 
ing from  severe  anemia,  loss  of  weight  and  strength.  If  these  condi- 
tions are  due  to  the  kidney  T.B.,  they  cannot  be  considered  as  contra- 
indications. Under  such  conditions,  it  might  be  possible  to  direct 
treatment  toward  improving  the  general  condition  of  the  patient  before 
performing  nephrectomy.  In  one  of  our  cases  a  gain  of  thirty  pounds 
was  obtained  by  the  patient,  after  instituting  proper  management. 

The  surgical  management  of  bilateral  tuberculosis  is  still  unsettled. 
In  a  few  instances,  the  more  diseased  of  the  two  kidneys  has  been 
removed,  in  the  hope  of  allowing  the  remaining  kidney  to  heal.  In  view 
of  the  fact  that  cases  of  tuberculosis  of  the  kidney  do  not  heal  under 
medical  treatment  when  the  disease  is  unilateral,  it  is  difficult  to  follow 


HEBMAN   L.    KEETSCHMEK,   M.D.  119 

the  logic  of  this  and  believe  that  the  remaining  kidney  will  heal.  It 
is  quite  conceivable,  in  certain  well  selected  cases  in  which  the 
process  is  in  its  incipiency,  with  only  a  slight  amount  of  destruction 
of  kidney  tissue,  whereas  the  opposite  kidney  may  be  the  seat  of  very 
advanced  tuberculosis.  Under  such  circumstances,  it  might  be  per- 
missible to  remove  the  kidney  which  is  the  seat  of  advanced  tuberculosis. 
However,  if  one  considers  nephrectomy  in  bilateral  kidney  tuberculosis 
from  the  standpoint  of  end  result,  I  think  nephrectomy  must  be  con- 
sidered a  palliative  measure  only. 


THE    SPECIFIC    ROENTGEN    MARKINGS    CHARACTER- 
ISTIC OF  PULMONARY  TUBERCULOSIS 

By  Kennon  Dunham,  M.D. 
cincinnati 

It  is  a  pleasure  to  come  to  Chicago  to  talk  to  you,  but  it  is  a  much 
greater  pleasure  to  bring  to  you  my  teacher,  Professor  Miller,  who  has 
shown  me  how  to  solve  the  big  problem — namely :  What  is  the  anatom- 
ical character  of  the  lesion  which  records  a  density  upon  the  Roentgen 
plate  characteristic  of  pulmonary  tuberculosis  ?  He  pointed  out  that  the 
only  way  to  find  the  answer  "was  to  remove  from  the  lung  the  part  caus- 
ing the  density  and  to  study  that  part  by  serial  sections. 

As  it  has  been  impossible  to  study  the  anatomy  of  the  lungs  by 
means  of  the  single  sections,  so  it  is  impossible  to  study  pathological 
anatomy  of  lungs  accurately  except  by  serial  sections.  Before  consid- 
ering the  pathological  anatomy  of  these  lesions,  let  us  first  take  up  the 
Roentgen  findings  which  I  consider  characteristic  of  pulmonary 
tuberculosis. 

To  be  able  to  see  this  density  definitely,  it  is  necessary  to  view  the 
Roentgen  plates  stereoscopically.  Then  we  see  a  triangular  area  of  in- 
creased density,  with  the  base  of  the  triangle  near  the  pleura  and  the 
apex  pointing  toward  the  hilus  and  connected  with  the  hilus  by  a  heavy 
trunk. 

These  trunks  are  seen  normally  in  the  healthy  chest  plate  passing 
out  from  the  hilus  and  are  definitely  located  as  shown  upon  the  screen. 
About  midway  into  the  parenchyma  of  the  lung  these  trunks  break  up 
into  finer  lines  which  normally  should  radiate  but  do  not  quite  reach 
the  pleura. 

The  early  changes  characteristic  of  tuberculosis  are  found  in  those 
fine  radiating  lines  which  I  have  termed  the  linear  markings.  Thus  we 
have  the  hilus  shadows  and  the  trunks  leading  from  them  which  break 
up  into  the  linear  markings. 

Great  variation  is  seen  in  these  triangular  areas  both  with  regard 
to  the  character  and  degree  of  the  density  of  their  markings.  This  is 
determined  by  the  age  and  extent  of  the  lesion.  Thus  we  can  usually 
decide  definitely  what  part  of  the  lung  was  first  affected,  because  in 
that  part  we  will  have  the  greater  density.  As  tuberculosis  usually 
starts  in  the  parenchyma  beyond  some  one  trunk  much  earlier  than  it 
makes  its  second  invasion,  we  have  a  second  characteristic  picture  of 
tuberculosis  on  the  Roentgen  plate,  i.  e.,  an  uneven  distribution  of  in- 
creased densities  in  contrast  to  the  homogeneous  changes  which  are 
found  in  other  conditions,  such  as  senility  and  certain  forms  of  heart 
disease. 

In  the  past  the  Roentgen  diagnosis  of  pulmonary  tuberculosis  has 
rested  upon  changes  of  density  in  the  hilus  and  the  heavy  trunks. 

120 


KENNON   DUNHAM,    M.D,  121 

These  were  read  from  the  single  plates,  but  such  readings  could  not 
be  made  to  correlate  with  the  physical  condition  of  the  patient  or  with 
careful  physical  findings. 

Today  I  wish  to  show  you  that  the  earlier  changes  take  place  in  the 
linear  markings.  And  further,  I  wish  to  show  you  that  these  changes 
are  due  to  tubercles  scattered  along  the  finer  branches  of  the  bronchial 
tree.  These  conclusions  are  based  upon  more  than  three  thousand  care- 
fully examined  chests  of  which  the  readings  of  Roentgen  plates  and  the 
physical  examinations  were  carefully  recorded.  The  work  has  been 
checked  up  by  more  than  three  hundred  autopsies.  A  few  of  these 
lungs  have  been  carefully  studied  by  Dr.  Miller  and  myself  to  ascertain 
exactly  what  pathological  lesions  caused  the  Roentgen  densities.  We 
found  these  early  changes  were  due  to  myriads  of  tubercles — not  one 
nor  a  few — but  myriads  of  tubercles  scattered  along  the  bronchial  tree, 
and  that  they  reached  completely  to  and  into  the  pleura.  Thus  we  have 
been  able  definitely  to  connect  the  Roentgen  findings  with  a  definite 
pathological  condition.  For  a  long  time  this  was  not  easy  to  under- 
stand, because  this  definite  distribution  of  the  tubercles  along  the  bron- 
chial tree  has  not  been  recognized  by  our  pathologists. 

This  paper  discusses  pulmonary  tuberculosis  involving  the  paren- 
chyma of  the  lung  in  people  twelve  years  of  age  or  over.  "We  are 
not  speaking  of  miliary  tuberculosis,  glandular  tuberculosis,  peribron- 
chial tuberculosis  or  tuberculosis  in  children.  We  are  speaking  of  the 
common  ordinary  disease  known  as  consumption,  the  kind  that  has  a 
first,  second  and  third  stage.  It  is  the  disease  that  exists  in  fully  ninety 
per  cent,  of  the  adults  having  lung  tuberculosis  that  come  to  our  offices, 
our  clinics,  and  are  filling  our  hospitals.  It  is  the  disease  which  we  are 
organized  to  fight,  and  about  which  these  plates  speak  to  us  so  plainly. 

By  means  of  the  stereo-roentgenograms  of  the  chest  we  can  recognize 
the  normal  chest  and  the  tuberculous  chest,  and  with  these  assured,  dif- 
ferential diagnosis  of  pulmonary  lesions  becomes  a  comparatively  easy 
matter.  Syphilis  gives  us  no  increased  density  except  in  rare  eases ;  the 
distribution  of  carcinoma  and  sarcoma  is  usually  very  distinct  from 
tuberculosis.  The  base  and  the  hilus  are  more  frequently  involved  and 
but  seldom  do  these  lesions  follow  the  trunks.  A  chronic  cough  which 
is  not  tuberculous  may  show  heavy  trunks  and  hilus  shadows  but  no 
change  in  the  linear  markings.  Either  influenza  or  pneumonia  may 
show  a  central  lesion  but  unless  a  large  area  is  involved  they  do  not 
reach  the  pleura  and  their  density  is  usually  more  evenly  distributed 
than  that  of  tuberculosis.  This  differentiation  should  not  be  made  from 
the  X-ray  plates  alone  but  from  the  history,  physical  condition  of  the 
patient  and  physical  findings,  and  other  laboratory  methods  must  be 
employed.  No  laboratory  method  will  do  away  with  the  necessity  of 
using  brains.  No  more  interesting  nor  accurate  study  can  be  made  from 
these  plates  than  the  location  of  the  initial  lesions  in  tuberculosis.  To 
repeat,  we  are  not  speaking  of  glandular  tuberculosis  but  are  speaking 


122  ROENTGEN  MARKINGS  IN  PULMONARY  TUBERCULOSIS 

of  parenchymal  tuberculosis.  Hippocrates,  Laennec,  Flint  and  our 
greatest  pathologists  have  found  initial  lesions  in  the  apices.  This  my 
X-ray  findings  confirm.  The  basal  lesion  dictates  a  grave  prognosis. 
It  is  very  rare  to  have  a  basal  lesion  without  extensive  and  older  apical 
lesions,  except  in  children,  and  these  do  not  reach  maturity.  Some- 
times you  wiU  find  an  early  lesion  in  the  apex  of  the  lower  lobe  but  this 
is  usually  associated  with  an  older  apical  lesion  of  the  upper  lobe.  It 
is  probably  true  that  the  right  side  is  more  frequently  involved  than 
the  left,  but  the  left  side  is  much  more  frequently  the  primary  seat  of 
infection  than  clinicians  have  realized.  This  is  because  tuberculosis 
gives  physical  signs  more  early  in  the  upper  right  than  in  the  upper 
left.  Normal  breathing  has  a'  more  bronchial  sound  in  the  upper  right 
than  in  the  upper  left.  This  is  because  the  vesicular  breathing  is  more 
modified  in  the  upper  right  by  the  sounds  from  the  trachea.  Slight 
lesions  increase  the  transmission  of  this  tracheal  sound  much  more  in 
the  upper  right  than  they  do  in  the  upper  left.  This  is  because  the 
trachea  lies  much  closer  to  the  upper  right  than  it  does  to  the  upper 
left. 

We  have  learned  from  the  X-ray  that  whispering  pectoriloquy  in  the 
upper  left  is  very  significant  of  tuberculous  changes,  and  that  the  pro- 
longed high-pitched  expiration  so  often  found  in  people  over  fifty  is 
also  of  great  significance ;  but  the  rales,  except  those  just  at  the  end  of 
inspiration,  frequently  do  not  mean  tuberculosis. 

As  I  have  previously  said  in  my  Stereo- Clinic :  To  men  who  have 
never  known  the  illumination  of  having  their  previously  uncontested 
physical  examinations  constantly  checked  up  by  the  bold  black  and 
white  of  stereo-roentgenograms,  the  claim  I  make  for  the  necessity  of 
their  use  seems  based  upon  an  inability  to  make  good  physical  examina- 
tions or  an  undue  enthusiasm  for  the  Roentgen  ray.  But  constant  use 
of  the  roentgenological  method  since  1909,  both  in  conjunction  with  my 
own  physical  examinations  and  those  of  some  of  the  ablest  men  in  the 
world,  as  well  as  with  post-mortems,  has  enabled  me  to  state  authorita- 
tively that  stereo-roentgenological  examination  of  the  chest  has  added 
that  scientific  element  to  the  study  of  tuberculosis  which  marks  another 
decided  advance  toward  the  understanding  and  the  elimination  of  this 
disease. 


THE  LYMPHATICS  AND   LYMPHOID   TISSUE   OF   THE 

LUNG  AND  THEIR  RELATION  TO  DISEASE 

PROCESSES 

By  W.  S.  Miller,  M.D. 
madison,  wis. 

The  anatomical  unit  of  the  lung  is  the  lobule.  Under  this  term  two 
different  areas  have  been  described: 

1.  Those  smaller  areas  composed  of  a  ductulus  alveolaris  (terminal 
bronchus),  the  air  spaces  connected  with  it,  and  their  blood  vessels, 
lymphatics,  and  nerves. 

2.  Those  larger  areas,  composed  of  groupings  of  the  above  defined 
lobules  with  their  blood  vessels,  lymphatics,  and  nerves,  which  are 
marked  out  in  lungs  that  possess  a  thick  pleura,  as  in  the  lung  of  the  ox 
and  that  of  man,  by  connective  tissue  septa. 

The  first  of  these  two  areas  is  also  known  as  the  primary  lobule ;  the 
last,  composed  as  it  is  of  groupings  of  primary  lobules,  form  the  sec- 
ondary lobules  which  in  turn  form  the  lobes  of  the  lung. 

AIR    SPACES 

It  is  not  my  purpose  to  enter  into  a  detailed  description  of  the  air 
spaces  of  the  lung ;  the  brief  bibliography  given  at  the  end  of  this  report 
will  refer  the  reader  to  the  recent  literature  on  the  subject. 

In  Figure  1  a  bronchiolus  respiratorius  (b.r.)  is  shown  dividing  into 
two  ductuli  alveolares  (d.al.)  one  of  which  is  carried  out  in  detail. 
From  the  distal  end  of  this  ductulus  alveolaris  three  atria  (a.a.a.)  arise, 
each  of  which  communicates  mth  a  variable  number  of  sacculi  alveolares 
(s.al.)  which  bear  around  their  periphery  the  alveoli  pulmonum  (a.p.). 

In  this  particular  diagram  the  lobule  is  represented  as  being  situ- 
ated immediately  beneath  the  pleura  (P.),  but  the  same  relation  of  air 
spaces  prevails  throughout  the  lung. 

BLOOD   VESSELS 

There  are  two  sets  of  blood  vessels  to  be  considered  in  connection 
with  the  lung:  the  bronchial  and  the  pulmonary.  The  former  are  the 
nutrient  vessels  of  the  lung;  the  latter  are  the  functional  vessels  of  the 
lung. 

Bronchial  artery.  The  bronchial  artery  is  distributed  to  the  walls 
of  the  bronchi,  the  connective  and  the  lymphoid  tissue  of  the  lung.  It 
also  supplies  the  lymphoglandulae  of  the  hilum.  In  those  lungs  which 
possess  a  thick  pleura  and  have  the  secondary  lobules  marked  off  by 
pronounced  septa  as  in  the  lung  of  the  ox,  the  sheep,  and  man,  the  bron- 
chial artery  extends  to  the  pleura  and  there  furnishes  a  special  blood 
supply  to  the  walls  of  the  lymphatics.     In  those  lungs  which  have  a 


124 


LYMPHATICS  AND  LYMPHOID  TISSUE  OF  THE  LUNG 


thin  pleura  as  the  lung  of  the  eat,  the  dog,  and  the  rabbit,  it  is  the  pul- 
monary artery  which  supplies  the  pleura  with  blood. 


Fig.  1.  Schematic  longitudinal  section  of  a  primary  lobule  of  the  lung  (ana- 
tomical unit)  showing  the  relation  of  the  blood  vessels  to  the  air  spaces  and  to  the 
pleura;  the  position  of  lymphoid  tissue  and  its  relation  to  the  air  spaces,  blood 
vessels,  lymphatics,  and  pleura.  Pulmonary  artery,  red;  pulmonary  vein,  blue; 
lymphatics,  black.    Further  explanation  is  given  in  the  text. 

Bronchial  veins.  True  bronchial  veins  are  found  only  at  the  hilum 
of  the  lung.  They  empty  into  the  vena  azygos,  the  vena  hemiazygos, 
or  one  of  the  venge  intercostales.  In  all  other  situations  the  blood 
brought  to  the  lung  by  the  bronchial  artery  is  returned  by  the  pul- 
monary veins.  There  are  no  anastomoses  between  the  bronchial  artery 
and  the  pulmonary  artery.  The  relation  of  the  bronchial  artery  to  the 
pulmonary  vein  will  be  taken  up  when  describing  the  origin  of  the 
pulmonary  vein. 

Pulmonary  artery.  The  pulmonary  artery  follows  in  all  of  its  sub- 
divisions the  subdivisions  of  the  bronchial  tree.  At  its  terminal  ending 
it  comes  to  occupy  a  central  position  within  the  lobule  (Fig.  1  art.  and 
Fig.  2)  dividing  into  as  many  branches  as  there  are  atria  connected 
with  the  ductulus  alveolaris  belonging  to  that  particular  lobule.     Each 


W.    S.    MILLER,    M.D. 


125 


atrial  artery  divides  into  branches  which  pass  to  the  sacculi  alveolares 
in  the  walls  of  which  they  break  up  into  the  capillary  network  of  the 
lung. 

Pulmonary  vein.  The  pulmonary  veins  arise  from  radicles  situated 
in  the  pleura  (Fig.  1;  1),  from  the  distal  end  of  the  ductuli  alveolares 
(Fig.  1;  2),  from  the  place  where  bronchi  divide  (Fig.  1;  3)  and  from 
the  network  of  capillaries  into  which  the  pulmonary  artery  breaks  up. 
While  the  pulmonary  artery,  as  already  stated,  occupies  a  central  posi- 
tion in  its  relation  to  the  lobule,  the  veins  are  situated  on  the  periphery 


Fig.  2.  Combination  of  three  sections  taken  through  the  center  of  a  primary 
lobule  of  the  limg  of  a  dog.  DA.,  Ductulus  alveolaris;  AAA.,  Atria;  A.S.,  A£., 
A.S.,  Sacculi  alveolares;  C,  Alveolus  pulmonis.  The  tunica  muscularis  of  the 
ductulus  alveolaris  is  indicated  by  the  broken  lines.  The  pulmonary  artery  is 
indicated  by  the  vessel  with  a  stellate  opening;  the  pulmonary  veins  are  in  solid 
black.  Note  the  two  veins  which  arise  from  the  ductulus  alveolaris;  they  correspond 
to  {2),  in  Fig.  1.    Camera  lucida  drawing. 


of  the  lobule  (Fig.  2).  There  is  a  single  exception  to  this  rule,  namely: 
those  veins  which  arise  from  the  distal  end  of  a  ductulus  alveolaris  (Fig. 
1;  2)  are  situated  within  the  lobule  (Fig.  2).  The  blood  brought  to 
the  bronchi  and  the  connective  tissue  of  the  lung  is  returned  by  the  veins 


126  LYMPHATICS  AND  LYMPHOID  TISSUE  OF  THE  LUNG 

which  have  their  origin  at  the  place  where  the  bronchi  divide  (Fig.  1; 
3)  and  from  the  distal  end  of  the  duetuli  alveolares  (Fig.  1;  2). 

LYMPHATICS  . 

If  the  preceding  description  of  the  blood  vessels  has  b-  i^n  thoroughly 
understood  the  description  of  the  lymphatics  will  be  easily  compre- 
hended, for  they  follow  closely  the  distribution  of  the  blood  vessels. 

Lymphatics  of  the  hronchi.  The  lymphatics  form  within  the  walls 
of  the  bronchi  a  rich  network  which  extends  throughout  the  entire 
bronchial  tree.  This  network  communicates  freely  with  the  network  of 
lymphatics  which  accompany  the  pulmonary  artery;  it  also  gives  origin 
to  lymphatics  which  leave  the  bronchi  at  the  place  where  they  divide 
(Fig.  1;  3)  and  at  the  distal  end  of  the  duetuli  alveolares  (Fig.  1:2), 
accompanying  the  veins  which  arise  at  the  same  place.  Beyond  the 
duetuli  alveolares  no  lymphatics  are  found ;  in  other  words,  no  lym- 
phatics are  present  in  the  walls  of  the  air  spaces. 

Lymphatics  of  the  pulmonary  artery.  The  larger  branches  of  the 
pulmonary  artery  are  accompanied  by  two  or  three  main  lymphatics, 
which  are  so  arranged  that  one  of  them  lies  between  the  artery  and  the 
bronchus.  These  main  trunks  are  connected  by  numerous  loops  and 
there  is  thus  formed  a  network  with  a  long  mesh.  The  smaller  divisions  of 
the  artery  are,  as  a  rule,  accompanied  only  by  a  single  lymphatic.  The 
bronchial  lymphatics  and  the  arterial  lymphatics  are  in  communication 
with  each  other  at  the  place  where  bronchi  divide  and  at  the  distal  end 
of  the  duetuli  alveolares. 

Lymphatics  of  the  pulmonary  veins.  I  have  just  stated  that  the 
bronchial  lymphatics  and  the  arterial  lymphatics  communicate  with  each 
other  at  the  distal  end  of  the  duetuli  alveolares  and,  somewhat  earlier, 
that  lymphatics  also  left  the  bronchial  network  at  the  same  place  and 
passed  to  the  two  small  veins  which  arise  from  the  duetuli  alveolares 
at  this  point  (Fig.  2).  If  we  follow  these  lymphatics  we  find  that  they 
join  the  network  of  lymphatics  about  one  of  the  venous  trunks  on  the 
periphery  of  the  lobule  (Fig.  1;  2).  The  lymphatics  that  leave  the 
bronchi  at  the  place  where  they  divide  follow  the  veins  that  arise  at  the 
same  place  and  eventually  join  the  lymphatic  network  about  one  of  the 
main  venous  trunks  (Fig.  1;  3).  The  lymphatics  about  the  pulmonary 
veins  also  communicate  with  the  pleural  lymphatics  (Fig.  1;  1).  While 
throughout  the  lung  the  lymphatics  are,  as  a  rule,  destitute  of  valves, 
a  valve  is  present  at  the  junction  of  the  venous  (deep)  lymphatics  with 
the  pleural  (superficial)  lymphatics.  This  valve  opens  towards  the 
pleura. 

Lymphatics  of  the  pleura.  In  the  pleura  there  is  a  very  rich  net- 
work of  lymphatics  which  contain  numerous  valves.  This  network  com- 
municates with  the  deep  lymphatics  of  the  lung  which  extend  to  the 
pleura  along  the  pulmonary  vein,  but  the  presence  of  valves  at  the  point 


W.   S.    MILLER,   M.D.  127 

of  union  permits  of  lymph  flow,  or  injection  masses,  in  only  one  direc- 
tion. It  is  only  in  occasional  instances  that  the  valves  can  be  forced 
and  injections  made  to  enter  the  deep  lymphatics  from  the  superficial 
network.  Previous  statements  that  I  have  made  on  this  point  have 
been  misconst]  aed,  possibly  because  the  authors  have  been  as  unmind- 
ful of  the  purpose  of  valves  as  was  Fabricius  ab  Aquapendente. 

Direction  of  lymph  flow.  In  the  lymphatics  of  the  bronchi,  of  the 
arteries,  of  the  main  venous  trunks  and  the  greater  part  of  the  pleura, 
the  flow  is  towards  the  hilum  of  the  lung.  In  the  lymphatics  about  the 
veins,  the  flow,  in  those  vessels  which  are  situated  just  beneath  the 
pleura  and  communicate  with  the  pleural  network  of  lymphatics,  may 
be  towards  the  pleura.  This  probably  explains  why  we  may  find 
tubercles  in  the  pleura  and  none  in  the  deeper  part  of  the  lung. 

Cunningham  has  recently  demonstrated,  from  the  embryological 
standpoint,  that  the  lymphatics  coming  from  the  pleura  covering  the 
inferior  half  of  the  lower  lobe  pass  through  the  ligamentum  pulmonale 
and  drain  into  preaortic  lymph  nodes..  I  am  free  to  confess  that  I  have 
missed  these  lymphatics  in  the  adult,  though  "Willis  figured  them  in  his 
illustration  of  the  pulmonary  lymphatics,  published  in  1675.  Their 
course  corresponds  to  the  distribution  of  the  bronchial  artery  as  I  have 
found  it  in  the  ligamentum  pulmonale  of  the  sheep. 

LYMPHOID   TISSUE 

The  distribution  of  lymphoid  tissue  within  the  lung  and  the  relation 
which  it  bears  to  the  air  passages,  the  blood  vessels,  the  lymphatics  and 
the  pleura  should  interest  not  only  the  pathologist,  but  also  the  clinician, 
for  these  masses  frequently  serve  as  centers  to  which  disease  processes 
may  be  conveyed  through  the  lymph  stream. 

Along  the  larger  divisions  of  the  bronchial  tree,  true  lymph  nodes 
have  been  described  and  figured  by  a  number  of  investigators.  In  each 
instance  they  were  found  in  the  angle  formed  by  the  dividing  bronchi. 
In  the  normal  bronchioli  respiratorii  and  ductuli  alveolares  I  have  failed 
to  find  lymph  nodes  or  lymph  follicles,  but  have  found  masses  of  lymph- 
oid tissues  which  were  situated  between  the  muscle  coat  and  the  accom- 
panying branch  of  the  pulmonary  artery. 

As  we  have  seen  in  connection  with  the  lymphatics,  the  place  where 
bronchi  divide  and  the  distal  end  of  the  ductuli  alveolares  are  important 
landmarks ;  so  here  we  find  small  masses  of  lymphoid  tissue  in  the  same 
situation  and  bearing  a  direct  relation  to  the  lymphatics  which  arise  at 
these  points  (Fig.  1;2,  3).  If  we  follow  the  veins  and  their  accom- 
panying lymphatics,  which  arise  at  these  points,  to  their  junction  with 
the  venous  trunks  and  the  accompanying  lymphatics,  there  will  be 
found,  in  the  angle  formed  by  the  union  of  the  two  veins,  lymphoid 
tissue  (Fig.  1;  2,  3).  Veins  which  arise  from  the  capillary  network  in 
the  walls  of  the  air  spaces  do  not  possess  lymphatics  or  lymphoid  tissue. 


128 


LYMPHATICS  AND  LYMPHOID  TISSUE  OF  THE  LUNG 


When  lymphoid  tissue  is  present  along  the  course  of  the  pulmonary 
artery  it  does  not,  in  normal  lungs,  form  the  sheath-like  arrangement 
described  by  some  authors,  but  is  found  as  small  masses  situated  be- 
tween the  artery  and  air  spaces  rather  than  between  the  artery  and 
bronchus. 

In  the  pleura  we  always  find  a  small  mass  of  lymphoid  tissue  asso- 
ciated with  the  place  where  the  radicles  of  the  pulmonary  vein  unite 
to  form  a  venous  trunk,  and  the  lymphatics  associated  with  the  venous 
trunk  join  the  pleural  network  of  lymphatics  (Fig.  1;  1).  The  amount 
of  lymphoid  tissue  present  at  this  point  varies  with  the  age  of  the  indi- 
vidual and  the  amount  of  pigment  present;  being  increased  in  amount 
the  older  the  individual  and  the  greater  the  quantity  of  pigmentation. 

Lymph  nodes  and  lymph  follicles  have  been  described  as  present  in 
the  pleura.  I  can  not  recognize  them  as  normal  structures.  They  are, 
in  my  opinion,  always  pathological,  taking  their  origin  from  the  pres- 
ence of  irritating  substances,  like  particles  of  carbon;  or  as  an  hyper- 
plasia of  already  existing  lymphoid  tissue,  as  in  leucaemia.  In  the  latter 
case  pigmentation  is  usually  absent. 

For  the  correct  interpretation  of  roentgenograms,  definite  knowledge 
of  the  distribution  of  the  bronchi,  the  arteries,  the  veins,  the  lymphoid 
tissue,  the  lymph  follicles  and  lymph  nodes  within  the  normal  lung  and 
at  the  hilum  is  absolutely  necessary;  for  it  is  impossible  to  correctly 
understand  the  pathological  without  a  previous  knowledge  of  the  normal. 


BIBLIOGRAPHY 


Cunningham,  R.  S. 
MiUer,  W.  S. 


In  Proc. 


Anatomical  Record.     Vol.  9,   1915. 

Amer.  Assoc,  of  Anatomists. 

Journ.  Morph.    Vol.  8,  1893. 

Archiv.  f .  Anat.  u.  Physiol.   Anatom.  Abt.  1900. 

Amer.  Journ.  Anatomy.     Vol.  7,  1908. 

Anatomical  Record.    Vol.  5,  1911. 

Journ.  Morph.     Vol.  24,  1913. 

Reference  Handbook  of  the  Medical  Sciences, 
3rd  edition.     Vol.    6,    1916.     For    extended 
literature  see  the  2nd  edition. 
Note.     The  above  report  was  illustrated  by  a  series  of  forty-six  lan- 
tern slides,  demonstrating  the  various  points  touched  upon. 


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